The right-hander looks to avenge that defeat in Wednesday night's decisive series finale at AT&T Park.
Again calling the area home for the first time since spending his first six seasons (1999-2004) with Oakland, Hudson (3-1, 2.19 ERA) has been San Francisco's most effective starter. He held Cleveland to a run and four hits over seven innings in a 5-1 victory Friday for his latest quality start.
"He's a veteran guy," Cleveland's Nick Swisher told the Giants' official website. "So if you go out there a little too geeked up, he knows exactly what he's doing."
Hudson, who became the first Giants starter to work at least seven innings in each of his first five outings since Livan Hernandez's six-game streak in 2002, allowed two walks Friday after going 30 2-3 innings without yielding one.
"Luckily for me I've been able to locate and stay down in the zone," he said. "Guys have made some really good plays behind me and as a result I've been able to get some pretty quick outs so far this year."
Hudson is 5-2 with a 1.82 ERA in his last nine starts against the Padres, but those defeats came in the two most recent outings. He allowed two runs and a season-high eight hits over seven innings of a 3-1 loss at San Diego (13-15) on April 19.
He'll have a tough act to follow after Yusmeiro Petit threw six strong innings during an emergency start in San Francisco's 6-0 victory Tuesday. Petit got the call when scheduled starter Matt Cain cut his finger prior to the game.
Angel Pagan and Buster Posey each hit first-inning homers for the Giants (16-11), who bounced back from Monday's 6-4 loss to win for the fifth time in six contests.
Posey is 6 for 14 with two homers in four games after he went 3 for 36 in his previous 12 contests. He's 3 for 6 with a home run against San Diego starter and Oakland native Robbie Erlin (1-3, 6.35).
Making his first appearance in the Bay Area, the left-hander looks to avoid a fourth straight losing start. Erlin yielded a run in six innings of a 2-1 win at Cleveland in his first start April 9, but has given up 15 over 16 innings of the last three.
That includes April 20 against the Giants as he gave up four runs and walked three in six innings of a 4-3 defeat. Erlin followed that performance by allowing eight runs and 13 hits over 5 1-3 innings of an 11-1 loss at Washington on Friday.
"It all starts with the fastball," manager Bud Black told the Padres' official website. "That's the pitch you're going to throw the most. He just didn't throw enough good, quality strikes."
Shut out for the fourth time this season and second in four games, the Padres totaled three hits Tuesday, including a double from reliever Donn Roach.
San Diego's Cameron Maybin is 6 for 16 with a homer versus Hudson. However, he's 1 for 8 with three strikeouts after going 2 for 4 at Washington on Sunday in his season debut following a biceps injury.
The Padres have dropped 20 of 29 at San Francisco since last winning a series there Oct. 1-3, 2010.