The move is retroactive to April 4.
The team recalled right-hander Chris Heston from Triple-A Sacramento, with Heston getting the start in the team's series finale against the Arizona Diamondbacks on Wednesday.
Giants manager Bruce Bochy said he expects it will be a two-week injury for Cain, who is making his fifth trip to the DL in the last two seasons.
Following a four-year stretch when he averaged 33 starts, posted a 2.93 ERA and made three All-Star teams, Cain has dropped off recently. He slipped to a 4.00 ERA in 2013 and made only 15 starts in 2014 before being shut down in August to undergo elbow surgery.
Cain joins Jake Peavy as the second starter to miss the start of the season, as Peavy will miss his scheduled start on Tuesday with back stiffness.
The Giants have split the first two games of their series with Arizona.
- Alex Putterman and Scooby Axson