Nolasco will seek to lead the Marlins to a ninth straight win in San Francisco on Friday night while improving to 5-0 there all-time.
The Giants (37-35) entered Thursday's series opener having batted .320 while scoring 59 runs in their prior 11 games. San Francisco, though, was limited to four hits in a 2-1 defeat to Miami (23-49).
In his first career pinch-hit at-bat, the Marlins' Marcell Ozuna had a two-run single in the eighth inning to keep his team's win streak at AT&T Park intact. The victory was also their 11th in the last 15 overall matchups with the Giants.
"He's a pretty good pinch hitter," manager Mike Redmond said.
With Nolasco starting Friday, Miami would appear to have a good chance to beat San Francisco again. In eight career starts against the Giants, the right-hander is 5-3 with a 1.83 ERA - his lowest ERA against any team he has faced more than twice.
Nolasco, who has won four of his last five decisions in the series, is 4-0 with a 0.87 ERA in his four all-time games in San Francisco, easily his best showing in any stadium.
"I wish I could tell you what it was," he told the team's website. "If I knew what it was, I'd try to do it in every ballpark."
Nolasco (4-7, 3.61 ERA) is coming off only his second win in nine starts, a 7-2 victory against St. Louis on Sunday. He gave up one run and three hits over seven innings and got the rare benefit of some generous run support.
Nolasco had been given a combined seven runs in his previous eight starts.
"It helps a ton," he said. "It just changes everything and the way you pitch and your approach."
The Marlins don't appear poised to repeat that effort considering in four games since they're batting .171 and have scored eight runs. They also have to face Tim Lincecum (4-7, 4.57), who has pitched well this month but is still having trouble getting enough support from his teammates.
The right-hander has posted a 2.55 ERA in his last three outings but is 1-2. He allowed three runs in six innings against Atlanta on Sunday and was saddled with a 3-0 loss.
Lincecum has received a combined four runs in his last six games and none in each of his past two.
"I was proud of how he battled out there," manager Bruce Bochy told the team's website. "He didn't let the game get away from us. He ended up throwing a pretty good game. We just didn't do anything with the bats."
Lincecum is 2-1 with a 3.67 ERA in four career starts against the Marlins but gave up six runs over 5 2-3 innings in his most recent matchup, a 7-6 defeat in Miami on May 25, 2012.
San Francisco's Joaquin Arias, currently riding an 11-game hit streak, went 0 for 3 in his only matchup against Nolasco last season.