The prologue of the book shows us yet unnamed man, who gets a parcel via mail as his birthday gift. In the parcel, there is a dried and framed flower – similar to those he got every birthday before. This one is the 44th. But this time the man - who we learn is named Henrik Vanger - calls a detective to solve the mystery of these flowers. Superintendent Morrel tries to figure out who is the mysterious sender but neither he, nor the owner of the flower don’t have any clue to their personality. This powerlessness makes Vanger cry.
After the prologue we are transferred to Stockholm, Sweden, to December, 2002. There we meet another character of the story: Mikael Blomkvist, a financial journalist and publisher of the Swedish political magazine Millennium. He is very eager to fight the financial corruption and illegal deals but he has just lost a trial against the billionaire entrepreneur Hans-Eric Wennerström. Now he is accused of publishing false and offending information and is sentenced to three months in prison and a huge fine.
Then we meet another character, Lisbeth Salander. She is 24 years old but Lisbeth is already renowned private investigator with excellent reputation. Her boss, Dragan Armansky, who she works with in Milton Security, arranges the meeting with Dirch Frode. Dirch is a lawyer of Henrik Vanger, a legendary Swedish industrialist (who we met in the prologue already). Dirch hired Milton Security to compile a detailed biography of Blomkvist. Salander reads her report, saying that Blomkvist is divorced, has a daughter and now is in a relationship with married Erika Berger, his editor, whose husband doesn’t mind her having an affair. The conclusion of the report is that Blomkvist is, generally, an honest person and good journalist and it seems that Wennerström framed him. Frode offers her to investigate Wennerström also and Lisbeth agrees.
Blomkvist, in the meanwhile, is spending the weekend making love with Erika and asking her to fire him temporarily, so his trial will affect the journal less. Erika agrees, seeing this as a good way to solve Blomkvist’s problem. Later he receives a call from Dirch with an offer from Henrik to meet in Hedestad, Hedeby (Henrik himself is too old to travel anywhere). Dirch says that Henrik wants to hire the journalist but more details can be given only at the meeting. Blomkvist accepts this offer.
It’s Christmas Eve, so most of the characters visit their families and relatives. Lisbeth comes to her elderly mother in the nursing home. They discuss Salander’s sister, Camilla, who disappeared somewhere and didn’t visit them for a long time. Lisbeth’s mother’s conscience is dim and she mistakes Lisbeth for Camilla, not sure which of her daughters is visiting her. Blomkvist meets with his daughter, as well as his ex-wife and sister before temporarily moving to Hedeby.
Arriving to Hedestad, the journalist meets with elderly Henrik Vanger, who is now retired, transferring all the business to his son Martin. Henrik asks him for help in writing a family chronicle. There is one blank page in the whole story - the disappearance of his great-niece Harriet, granddaughter of his brother and former Nazi Harald, which happened here, in Hedestad. Harriet was sixteen years old and she vanished without leaving a trace 40 years ago, in 1966. Henrik is sure she was killed and he suspects some of the other members of Vanger family of committing that crime. Harriet had a habit to give dried flowers to him since she was eight, but even after her disappearance and, perhaps, death, someone continues to send the flowers to him. Henrik offers not only a decent sum of money but some previously unknown evidence against Wennerström. Blomkvist isn’t sure about whether to accept this offer - he is a journalist, not a detective - but finally he agrees and stays at Hedeby to investigate the case.
At the same time, back in Stockholm, Lisbeth secretly enters the Wennerström’s apartment building. Using her extraordinary technical skills she finds the wires going to his apartment and then asks her friend, a hacker nicknamed Plague, to sell her a special device to intercept all the information going through these wires. From now on we, as readers, follow the two plot lines - of Blomkvist and Salander.
Returning to Hedeby we learn that Blomkvist finds a list of five female names and five-digit numbers written by the missing Harriet Vanger. He meets with every living members of Vanger family, in order they are mentioned in family chronic. He starts from old and secluded Harald, his wife Isabella, who seem to be neglecting parents and their daughter Cecilia. Then he goes to the house of Martin, the current CEO of Vanger corporation. He befriends him and even is invited to the dinner. Martin says that the day Harriet disappeared he was trapped on the other side of the island because of the broken bridge. He also tells that his and Harriet’s father, Gottfried, died the year before Harriet disappeared.
Meanwhile, Lisbeth Salander, who happens to be mentally unstable and has a guardian attached to her since she has reached the age of 18, gets a new one - the lawyer called Niels Bjurman. But, unlike her previous guardian, who helped her to get a relatively normal life and a job, Bjurman starts from taking control of her communications and bank accounts and also talks about her private life in the manner that reminds of interrogation. When Lisbeth’s computer breaks, she asks Bjurman to give her some money to buy a new one, but he demands her to perform oral sex for that money, raping her orally after she refuses. He gives her the money after all, but Salander is seriously planning his murder. However, later she comes with a better plan of getting her control back and also humiliating her offender. The rapes continue.
On Hedeby Blomkvist receives an unexpected hint from his daughter. The religious teenager speaks to him about the Holy Bible and accidentally leads him to the verses describing the brutal punishments of the women for their sins. These verses are numbered the same way as the names in Harriett’s list. In the meanwhile, he has an affair with Cecilia breaking up with her when it’s time for him to return and serve his sentence.
Lisbeth manages to hide the camera in her backpack and films what Bjurman does with her, blackmailing him later. But the enraged lawyer chains her to the bed and rapes even more violently than before, leaving the young woman almost unconscious. Nevertheless, Salander makes another try, this time she has a Taser and is much better prepared. She shocks Bjurman, ties him to the bed like he did to her before and tortures him, gleefully explaining how the things will work from now on. She leaves after tattooing the words: “I am a sadistic pig, a pervert and a rapist” on his body.
After exiting the jail, Blomkvist renews his relationship with Cecilia. But after the affair is revealed to Erica, enraged Cecilia goes away, this time without a chance to start anew. Blomkvist instead ignores both of them, channeling all his energy to the investigation. He makes a big progress but then gets stuck and connects Dirch for help. Dirch recommends Salander as one of the best specialists he knows and arranges their meeting. Lisbeth agrees to work together with Blomkvist. United, they carry out an investigation and reveal who were the women mentioned in Harriet’s list. They all were murdered in between 1940s and 1960s in Sweden. This discovery leads them to the idea that shortly before her disappearance Harriet found a trail of a serial killer. The way of killing the victims was always all the same, eerie and resembling a ritual involving also animal sacrifices. During the investigation, Salander understands that she likes Blomkvist and they become lovers.
Once someone tries to shoot Blomkvist but he manages to remain safe. Neither he nor Salander can find who planned the unlucky assassination. Soon the journalist comes into conclusion that the killer of the women was Gottfried Vanger, Martin’s and Harriet’s father. But something is amiss, the last murder was conducted a year after Gottfried’s death, and later the journalist starts suspecting Martin also. The proofs supporting it are some family photos and evidences showing that Harriet was afraid of her brother.
Blomkvist returns to Hedeby to confront Martin and accuse him of murders. There he realizes he was right in the most painful way - Martin catches him in a trap, chains him in the basement and decides to show some cruel mercy, satisfying Blomkvist’s curiosity before raping and killing him, too.
The first serial killer in the Vanger family was really Gottfried. Until his death in 1965 he raped, tortured and killed women, encouraging his son to follow his steps. Both of them raped Harriet since she was 14 and in roughly the same age Gottfried raped Martin himself. The last murder in Harriet’s list was the first one for Martin.
When Martin is about to start torturing Blomkvist, Lisbeth breaks into the house and beats him with the golf club. She and the journalist escape riding her motorcycle. Martin chases him by car, but gets into a car accident and dies.
While Blomkvist is still recovering from the traumatic experience, Salander returns to Martin’s house, takes photos and destroys some evidences that can let the police to track her and Blomkvist. She also informs her boss about the result of investigation and demands he doesn’t tell anyone that she and Blomkvist are involved. Later the couple continue their investigation and discover that Harriet herself is alive.
Blomkvist manages to find her in Australia. She escaped there with the help of her cousin Anita (who lives in London now, also having fled from the native island). Finally Harriet tells him the end of the story. It was she who killed her father for raping her. But Martin learned that and used it to make her his sex slave. Anita helped her to run away as far as Harriet only could. In Australia Harriet lived under the name of her cousin, met her husband and now has three kids and a happy life. It was also she who sent flowers to Henrik, hoping that her grandfather would understand she is alive and well. Blomkvist persuades her to return to Sweden, to reunite with Henrik and to take the CEO position instead of her dead brother.
Henrik keeps his word, but the evidence against Wennerström that he offers turns out to be useless. Blomkvist is enraged. Then Salander returns to the hacking device placed on the wires in Wennerström’s apartments and analyses the information gathered there finding something much worse. Using this information, Blomkvist writes an expository article and a book about Wennerström. His magazine becomes successful on a national scale. Salander herself successfully steals $260 million from Wennerström’s accounts and transfers them to her anonymous offshore accounts.
Wennerström runs away and hides somewhere abroad. Lisbeth tracks him and then anonymously reports his location to the criminals, to whom he owes money. Soon Wennerström is found dead.
Lisbeth and Blomkvist spend Christmas together in his house. On New Year's Eve Salander unexpectedly comes to Blomkvist with a gift, intending to confess that she loves him and wants more than just sex and common work, but he is at his home with Erica Berger. Disappointed, Salander throws her gift in the trash and leaves.