The Sons of Anarchy star will join confirmed cast members Charlie Hunman and Idris Elba, Variety reports.
Day will play a professor in the film, which depicts the battle between humans and sea monsters on Earth towards the end of the 21st century.
The project will see humans fighting off the creatures emerging from the Pacific Rim with super-intelligent, large-scale robots.
The movie will be del Toro's first in three years, after Universal refused to fund his HP Lovecraft adaptation At the Mountains of Madness.
Day will next be seen alongside Jennifer Aniston and Colin Farrell in comedy Horrible Bosses.
Watch the trailer for Horrible Bosses below: