The Mariners (31-42) earned their first victory in five games against the last-place Padres (25-47) this season. The teams play the decisive series finale on Sunday afternoon in their last Interleague game of the season. The Padres are currently 7-7 in Interleague Play.
Hernandez's two-out, two-run double in the second gave the Mariners a 3-1 lead.
"I just left a sinker a little bit up," Marquis said. "He stayed inside the ball and hit it down the first-base line. If that pitch is a little bit down where I was trying to execute it, he hits it on the ground and it's a different result."
Hernandez improved to 4-for-27, with seven RBIs in his career.
"I was just trying to swing at the first pitch," he said. "I knew it'd be a fastball, and I wanted to hit it good."
Before Hernandez's two-run double, the Mariners tied the game 1-1 in the second on Brendan Ryan's bases-loaded groundout. The Mariners loaded the bases following a single, a walk, a fielder's choice and second baseman Logan Forsythe's throwing error.
The Mariners tacked on runs in the third and fourth. Michael Saunders hit his eighth home run -- a solo shot -- off of Marquis in the third, and Ichiro Suzuki had an RBI single in the fourth.
Marquis (1-3, 5.67 ERA) allowed five runs (two earned), struck out six and walked three in seven innings.
He has allowed 11 runs (six earned) in 26 1/3 innings with the Padres since the Twins released him.
"Maybe not his best command of pitches, but yet he went seven innings and gave us what we needed there as far as length," Padres manager Bud Black said. "He kept us relatively in the ballgame. The one mistake to Felix came back to haunt us."
Hernandez (5-5, 3.36 ERA) threw six scoreless innings after allowing a run on two singles and a balk in the first inning. Overall, he allowed a walk and six hits in seven innings. He pitched the 18th double-digit-strikeout game of his career, and the second of this season. It was his highest strikeout total since he struck out 12 on April 19 against the Indians.
"It was nice to finally get a win off these guys," Saunders said. "Felix threw the ball like Felix can. Whenever he takes the mound, we feel like we've got a really good shot at getting a 'W' that day. It all starts with starting pitching and he helped himself out [with the double]."
The Padres beat Hernandez the last time they faced him, scoring five runs in six innings against the right-hander on June 12 in Seattle.
"He threw some very good curveballs," Black said. "They were tight with good rotation. If there was one thing that stuck out tonight, it was the curveball. He was a little crisper tonight than he was in Seattle."
Padres hitters struck out 13 times.
Down 5-1 in the fourth, the Padres put runners at the corners, but Everth Cabrera grounded into an inning-ending double play. The Padres also put two on in the seventh, but pinch-hitter Mark Kotsay lined into an inning-ending double play.
"It's part of baseball," Black said. "The other innings, Felix was tough. We hit the ball on the nose. They had guys there.
"We had our chances, hit the ball on the nose. It just didn't happen for us tonight."