On a journey to find the cure for a Tatarigami's curse, Ashitaka finds himself in the middle of a war between the forest gods and Tatara, a mining colony. In this quest he also meets San, the Mononoke Hime.

A large monster attacks Japan, but dies suddenly. While the people rejoice and bask in relief, the giant corpse left behind begins to slowly rot and bloat. If it explodes, the nation will be destroyed.