Dr. James Marcus, the founder of the Umbrella Corporation, had a daughter, Alicia, who was dying of progeria. Desperate to save her, Marcus uses the T-virus on her and others with the disease. After another child treated with the virus died and then reanimated as a rabid zombie, Marcus tried to have the program shut down. His partner, Dr. Alexander Isaacs, had Marcus killed by Albert Wesker, then adopted Alicia and took over the Corporation.

安布雷拉公司[伞公司]的创始人，詹姆斯·马库斯博士有个女儿艾莉西亚正在早衰死亡。马库斯几乎绝望，把T病毒用于给女儿和患有该病的别人治疗。在对另一个孩子施用该病毒治疗后，患者死掉又活过来立即成了僵尸，马库斯为此企图关闭该流程。他的商业伙伴亚历山大·艾萨克斯命令阿尔伯特·威斯克处死了马斯克，自己收养了艾莉西亚并接管了该公司。

After the events in Washington D.C., Alice awakens after being betrayed by Wesker. The Red Queen appears and tells Alice she has 48 hours to infiltrate the Hive, over 400 miles west on I-64 in Raccoon City. The Umbrella Corporation has developed an airborne anti-virus, which can kill every organism infected by the T-virus, but is waiting for the last few remaining humans to be wiped out.

哥伦比亚特区华盛顿事件后，爱丽丝经历威斯克的背叛后苏醒过来。红后出现并告知爱丽丝，她必须在48小时内潜入浣熊市蜂巢，蜂巢位于向西400英里之外的浣熊市I-64区。安布雷拉公司已经开发出了能空气传播的抗病毒，会杀死所有感染了T病毒的生物，目前正等着最后遗留的少数人类被消灭。

Enroute to Raccoon City, Alice is captured by Isaacs, learning the "Isaacs" she previously killed was a clone. She escapes his convoy and reaches Raccoon City, where she is ambushed by a group of survivors: Doc, Abigail, Christian, Cobalt, Razor, and Claire Redfield, who survived the attack on Arcadia. Isaacs' convoy approaches, trailed by a horde of zombies. Alice and the group defeat the convoy, retrieve Isaacs' few human captives and burn the horde, though Cobalt is killed. Alice and crew enter the Hive entrance, at the bottom of the crater from the nuclear bomb previously dropped on the city. Wesker, in control of the Hive, releases mutated guard dogs, killing Christian and a freed captive.

在去往浣熊市的路上，爱丽丝被艾萨克斯俘虏，认识到她原来杀死的那个艾萨克斯其实是个克隆人。爱丽丝逃脱他的护卫队到达浣熊市后被一群幸存者伏击，这些幸存者有道克、艾比盖尔、克里斯托、克波特、瑞泽、克莱尔·雷德菲尔德，他们是阿卡迪亚遭到攻击后的幸存者。艾萨克斯护卫队赶往这里，尾随了一大群僵尸。爱丽丝队伍击败了护卫队，收容了艾萨克斯的几个人类俘虏，焚毁了僵尸群，但克波特在战斗中丧生。爱丽丝队伍进入蜂巢入口，入口在之前浣熊市丢核弹炸的大坑底部。威斯克控制着蜂巢，释放了变异的警卫狗，杀死了克里斯托和一个自由了的俘虏。

The Red Queen appears to Alice and explains that her program is in conflict, as she can never hurt an Umbrella employee but also must value human life. She plays a video of Isaacs explaining to Umbrella's executives a plan to release the T-virus, cleansing the world of humanity; many of the rich and powerful, including the company executives, are stored in cryogenic capsules in the Hive, with the intention of rebuilding the world following the resulting apocalypse. The Red Queen warns Alice that someone in her group is helping Umbrella.

红后出现在爱丽丝面前，解释她的程序有冲突，因为她不能伤害安布雷拉雇员而且还要衡量人类生命。红后播放了一个影碟，艾萨克斯正给安布雷拉公司管理层解释他的计划，释放T病毒清理人类世界，很多富人和当权者包括公司管理者，用低温荚膜封藏在蜂巢里，毁灭世界后再重建。红后警告爱丽丝，她的队伍里有人正在帮助爱布雷拉公司。

The group encounters several traps, killing Abigail and Razor. Alice and Doc plant bombs throughout the Hive, from the leftover equipment of the original team to investigate the Hive. Alice confronts the real, tech-upgraded, Isaacs. Doc is revealed to be Umbrella's spy, and Claire is captured by Wesker. A cryogenic capsule opens, releasing Alicia Marcus, Umbrella's co-owner, and Marcus' daughter. Isaacs reveals to Alice that she is actually a clone of Alicia, before going on to explain his plan to eliminate the pair and assume control of Umbrella. Alicia fires Wesker, allowing the Red Queen to crush his legs with a security door. Doc tries to shoot Alice, but his gun is empty — as Alice had earlier deduced his treachery — and Claire executes him. After giving Wesker a deadman's switch to the primed bombs, Alice and Claire pursue Isaacs while Alicia uploads a copy of her childhood memories.
这群人遭遇了几个陷阱，艾比盖尔和瑞泽丧生。爱丽丝和道克在整个蜂巢部署了炸弹，从原队伍的遗留设备处一直到勘察蜂巢沿路[译注：原文有错误]。爱丽丝面对真实有技术装备的艾萨克斯。道克被暴出是安布雷拉安插[在幸存者中]的间谍，克莱尔也被威斯克抓住。一个低温荚膜打开，艾丽西亚·马库斯 出现，她是公司的合伙持有人，詹姆斯·马库斯的女儿。艾萨克斯首先揭示爱丽丝是艾莉西亚的克隆人，然后解释他计划除掉合伙人艾莉西亚完全掌控爱布雷拉。艾莉西亚煽动威斯克，让红后关闭安全门夹断他的腿。道克向爱丽丝开枪，但没有子弹--爱丽丝之前推断出他是叛徒--克莱尔击毙了道克。塞给威斯克一个死人开关[译注：不按着蜂巢就炸]后，爱丽丝和克莱尔追杀艾萨克斯，此刻艾莉西亚上传她童年记忆的拷贝。

Isaacs, Alice and Claire fight; Isaacs overpowers Claire and attacks Alice in the Laser Corridor, eventually defeating her, but she uses that moment to activate a grenade in his pocket. She escapes to the surface with the anti-virus, but Isaacs reboots and catches her before she can release it. Before he can kill her, the Isaacs clone (from the convoy) arrives and kills him, believing itself to be the original Isaacs, but the clone is then devoured by the undead. Alice releases the anti-virus, killing all of the undead around her before she passes out. Wesker simultaneously drops the deadman's switch, destroying himself, Alicia, the Hive, and the hibernating Umbrella elite.

艾萨克斯对抗爱丽丝和克莱尔，艾萨克斯战胜克莱尔，并在激光走廊里攻击爱丽丝最终获胜，但爱丽丝利用该时机触发了他口袋里的手雷。爱丽丝带着抗病毒逃到地面，但艾萨克斯复活并在爱丽丝投放抗病毒前抓住了她。在艾萨克斯杀死爱丽丝前，艾萨克斯的克隆人(来自护卫队)赶到，杀死了艾莎克斯，觉得自己才是真正的艾萨克斯，但克隆人又被僵尸吞没。爱丽丝释放了抗病毒，她倒下前杀死了她周围所有的僵尸。此刻，威斯克丢下了死人开关，毁掉了自己，艾莉西亚，蜂巢，休眠中的安布雷拉精英们。

Claire wakes Alice, who survived because the anti-virus killed only the T-virus within her body, not the healthy cells. The Red Queen uploads Alicia's childhood memories into Alice, granting her a childhood. Alice travels into Manhattan, saying that the anti-virus, carried only by the winds, will take years to reach all corners of the globe, and until it does, her mission is not finished.

克莱尔唤醒了爱丽丝，爱丽丝活了下来，因为抗病毒只杀死她体内的T病毒，而非健康细胞。红后给爱丽丝加载了艾莉西亚所有的童年记忆，给她赋予了童年。爱丽丝去曼哈顿旅行，[故事]声称抗病毒被风吹到世界各角落需要多年，在此结果前，爱丽丝的任务还没结束。