That might be a difficult task against Ian Kennedy, who hasn't lost to the Giants in nine straight starts.
Cain and the defending World Series champs will try to snap a five-game losing streak on Monday night when they open a three-game series against Kennedy and the Arizona Diamondbacks at Chase Field.
After a 9-4 start, slumping San Francisco (13-12) dropped its eighth in 12 games with a 6-4 loss at San Diego on Sunday.
"We haven't been playing so well,'' manager Bruce Bochy said. "We've been making mistakes that have hurt us in this little streak we are in.''
The Giants haven't lost six in a row since suffering seven straight defeats from June 26-July 2, 2010, and turn to Cain to get them back on track.
Cain (0-2, 6.59 ERA), though, is still searching for his first victory after pitching inconsistently over his first five starts. It's the longest he's gone winless to open a season since 2008, when he didn't get his first victory until his sixth start.
After allowing seven runs in six innings in a 7-2 loss at Milwaukee on April 18, Cain gave up three earned and five hits over six innings in a 6-4, 11-inning loss to Arizona on Tuesday.
"I thought he regrouped and threw the ball well," said Bochy, whose club dropped two of three to the Diamondbacks.
Cain has pitched well in this series, winning nine of 11 decisions with a 2.95 ERA over his last 14 starts.
The three-time All-Star, however, will have to do a better job keeping the ball in the park. He's allowed six home runs over his last three starts, including Paul Goldschmidt's two-run blast in the last meeting.
Arizona (15-10) appears to be playing with some confidence heading into this meeting after beating Colorado 4-2 at home on Sunday to take three of four from the Rockies.
The Diamondbacks have won five of six overall to move into a tie with Colorado atop the NL West.
Although Kennedy (1-2, 4.70) hasn't won since opening day, another game against the Giants could help the right-hander get back in the win column.
Kennedy is 5-0 with a 2.14 ERA over his last nine starts in this series, surrendering a run and four hits in six-plus innings in a 3-2, 10-inning win at San Francisco on Wednesday.
Kennedy will try to cool off Buster Posey after the reigning NL MVP extended his hitting streak to nine games with a two-run homer on Sunday. He's batting .400 with three home runs and nine RBIs during that stretch.
While Pablo Sandoval - who went 4 for 5 on Sunday - has batted .346 in 35 career games in Arizona, he's just 7 for 33 (.212) against Kennedy.
Goldschmidt leads the Diamondbacks with five homers and 18 RBIs, but he's just 4 for 16 with four strikeouts facing Cain.
Gerardo Parra, a .220 hitter against Cain, has a .340 average over a career-best 13-game hitting streak.