Hellboy, Clay, Abe and two other agents return to the sewers to find the Eggs. Abe jumps into a cistern to capture a cluster of eggs, but is attacked and badly injured by another Sammael. The two agents are attacked and killed by yet another Sammeal, which Hellboy chases after. Clay is left behind and winds up getting stabbed by Kroenen, who then apparently commits suicide. Hellboy chases Sammael into a subway station, finally killing him again by smashing the monster into an oncoming train. Hellboy returns, shocked to find his friends wounded.
Back at BPRD, Manning reveals that Abe will recover but Clay is too badly wounded and most likely will not survive the night. Manning and Hellboy clash, both angry about what has happened. Meanwhile, Liz has decided to come back to BPRD. Hellboy is in his room, struggling to write a letter for Liz that describes his feelings for her when Liz comes in and reveals that she is going on a date with Meyers. Hellboy is angry, but puts it aside and decides to follow them.
Broom is doing an autopsy of sorts on Kroenen, where he learns that Kroenen is over 100 years old and his body is badly mutilated (due to a form of masochism). When the professor leaves, Kroenen uses a type of clockwork mechanism to restart his heart and allows Rasputin into the BPRD. Rasputin confronts the professor, taunting him for not knowing Hellboy's true purpose or name. Broom responds that-as far as he is concerned- Hellboy's proper title is "Son." Rasputin grants Broom a glimpse into the future, where Hellboy is responsible for Armageddon. Kroenen then executes Professor Broom.
Meyers and Liz are still on their date (with Hellboy watching) when they are told what has happened. Hellboy is devastated by the loss, refusing to eat or speak for days. Manning takes over the BPRD (a job he does not relish) and announces that he will lead a team to Russia to find the source of Sammael's eggs.
In Russia, Hellboy re-animates a corpse with magic and gets directions to Rasputin's Mausoleum. The group is divided inside, with Liz & Meyers in one direction and Hellboy & Manning in another. Hellboy and Manning find Kroenen's hiding place, and Hellboy saves Manning's life by attacking Kroenen with his stone fist.
Kroenen attempts to lure Hellboy into a spiked pit, but Manning throws a gear at Kroenen, blocking his attack. Hellboy knocks Kroenen into the pit and kills him with a gigantic gear. Hellboy and Manning thank each other for their endeavors, having formed a type of mutual respect.
Liz and Meyers find the egg chamber. Hellboy joins them, but he is overwhelmed by Sammael duplicates. Liz begs Meyers to attack her, hoping that it will trigger her fire-powers. It works, and Sammael (eggs and doubles) are destroyed for good. But Rasputin and IIsa take the opportunity to capture Hellboy and his friends.
Rasputin wants Hellboy to use his "Right Hand of Doom" to finally free the Seven Gods of Chaos. Hellboy refuses, but learns that Liz is critically injured and may not survive. He agrees to Rasputin's terms and speaks his true name- "Anung-Un-Rama." Hellboy's horns suddenly grow to full length and he begins to breathe smoke, having embraced his "Demon" heritage.
Meyers is able to free himself before Hellboy opens the final seal of the Gods. Meyers begs Hellboy to remember who he is, and throws the prayer-beads that once belonged to Professor Broom. Hellboy remembers that he does not have to be evil; he has a choice- and his father died so he could make that choice. Hellboy rips off his horns and stabs Rasputin with them, stating that he doesnt' need Rasputin to tell him who he is. Rasputin's death unleashes a monster (the last envoy of the Seven Gods, called Behemoth) that quickly grows in size.
Hellboy gets Meyers and Liz out of the room, and Meyers gives him a weapon- a cluster of grenades intended for use on Sammael's eggs. Hellboy has a long fight with the Behemoth before finally getting the huge monster to swallow the grenades. A chain reaction yields a cacophony of explosions as Behemoth is enveloped in a cloud of fire, goo and soft flesh. Hellboy lands with a sickening, bone-crunching thud. With a bellow, Behemoth goes down, the limp tentacles missing Hellboy as they vanish in a blaze of energy and light. Finally, just a few cinders of flesh float in the air. Hellboy stands, covered in goo. Two final shockwaves of light ripple over the ground.
Hellboy lurches into the passageway and spots Myers, who says Liz has no pulse. Liz's body is on the floor. Hellboy kneels down and cradles Liz's head in his huge hand. Holds her against his powerful chest and whispers in her ear. A beat or two, then a moan. Liz opens her eyes and asks what he said. He looks at her, lovingly caressing her hair.
Hellboy responds that he was talking to those "on the other side," imploring them to give up Liz because he would gladly cross over himself to try and save her. A warm, gentle fire rims her body. Liz looks at Hellboy for the first time as what he is: the man she loves. Moved by his sentiments (and by the events of the last few days), the two kiss passionately. Liz's fire engulfs them both in moments, but Hellboy, being fireproof, is unharmed. The fire haloes them and builds.
Agent Myers smiles a sad smile, illuminated by the flames. Meyers stands on and concludes Professor Broom's earlier thoughts: "What is it that makes a man 'a man?' It's the choices he makes. Not how he starts things- but how he decides to end them."