The Girl Who Played with Fire is the second volume in Stieg Larsson's trilogy. The book opens with Lisbeth Salander remembering being strapped down to her bed in St. Stefan's Children's Psychiatric Clinic. The thoughts of Lisbeth setting fire to a car with a man inside seem somewhat surreal although they turn out to be true.

Lisbeth has been traveling around the world after having stolen three billion kronor from a business tycoon. It is strange for Lisbeth to live in any other way than a life of poverty but she makes the most of it. While Lisbeth is in Grenada she takes a 16 year old lover. She also encounters an American couple who fight constantly. The husband is abusive to his wife. Lisbeth realizes that the man intends to kill his wife to inherit $40 million. Lisbeth and her lover rescue the woman during a hurricane. The man turns up dead the next day.

Lisbeth returns to Stockholm after a year. She finds a new apartment and moves in. Lisbeth decides to give her old apartment to Mimmi, an old friend and lover. Mimmi gladly accepts.

Lisbeth realizes that she left without saying goodbye to anyone. This fact upset Armansky, Lisbeth's old boss. Armansky says he will not hire Lisbeth again. Lisbeth tries to convince Armansky that she no longer needs to work.

Blomkvist had continued to watch out for Lisbeth while she had been gone and is pleased to learn she has returned to Stockholm. Blomkvist has been working alongside Dag Svensson on an article and book that exposes many public officials in a sex trade scandal. Svensson's girlfriend, Mia, is working on another aspect of the case as fodder for her doctoral dissertation.

Things begin to change rapidly when Svensson and Mia end up murdered and Lisbeth's prints are on the murder weapon. It is also thought that Lisbeth murdered Nils Bjurman, her former guardian and the man who had raped and abused her while she had been under his care.

The entire story begins to tie into the sex trade scandal and a mysterious man named Zala. Gunner Björck, a member of Säpo, is exposed in Svensson's article and book. Björck agrees to give Blomkvist information on Zala, aka Alexander Zalachenko, if he is written out of the story and his involvement in the sex trade is not exposed. Later Björck realizes that he only has Blomkvist's word that he will not be exposed. Bjurman knew of Björck's involvement and there may be some record of it in Bjurman's papers. Björck calls Zala for help.

Lisbeth and Blomkvist are hot on the same trail. It is learned that Zala is Lisbeth's father and each wants to kill the other. Lisbeth is determined to ruin Zala once and for all. Zala ends up shooting Lisbeth and tells Niedermann, Lisbeth's half brother, to bury her. However, Lisbeth is not dead and makes one more attack on Zala.

Blomkvist arrives at the farmhouse where the showdown took place not long after Lisbeth collapses on the kitchen floor. Lisbeth, remarkably, is still alive. Blomkvist calls for an ambulance.