Liriano, who was dealt to the White Sox on July 28, held the Twins hitless for 6 2/3 innings before serving up a two-run blast to Trevor Plouffe after plunking Justin Morneau with two outs.
"When he's throwing his slider and his changeup over and his fastball like that, it's tough," Twins manager Ron Gardenhire said. "We've all seen it. We've seen him dominate teams. Just dominate them. So we've seen it on our side. But we've also seen him have trouble finding the strike zone, so anything Frankie does, we've seen it one way or another."
Liriano, who no-hit the White Sox on May 3, 2011, fell short of his second career no-no, but gave up just that one hit over seven innings with nine strikeouts and two walks.
Liriano said he didn't have a no-hitter on his mind this time around, as he was just trying to give his first-place team a chance to win.
"To be honest, I wasn't thinking about a no-hitter," said Liriano, who improved to 3-1 with a 5.10 ERA in 10 appearances with the White Sox since the trade. "I was trying to go deep in the game and throw less pitches each inning."
Their familiarity with Liriano didn't help the Twins, as his stuff was too good in his second career start against Minnesota. He's now 1-0 with a 2.77 ERA against the Twins.
"He threw his offspeed pitches for strikes and when he can do that, he's effective," said catcher Drew Butera, who caught Liriano 31 times in his career. "He had a good slider and changeup today and it allowed him to throw his fastball inside and run the two-seamer when he needed to."
He outpitched Twins right-hander Samuel Deduno, who struggled with his control. Deduno, making his 13th start, gave up four runs on three hits and five walks over just four innings.
"My mechanics were OK, but I was just trying to do too much," Deduno said. "Nothing was working. But sometimes that's just part of the game."
The White Sox scored early, as Paul Konerko brought home the first run on an RBI groundout in the first inning after Kevin Youkilis walked and advanced to third on a single from Adam Dunn.
Konerko later crushed his 23rd homer in the third inning on a 2-1 fastball from Deduno. The two-run shot came after Deduno walked Dunn with two outs.
Chicago scored again in the fourth, when Dayan Viciedo walked, reached second on Deduno's second wild pitch of the game and scored on a two-out single from Gordon Beckham.
Former Twins reliever Jesse Crain struck out two in a scoreless eighth.
After the White Sox scored a run in the ninth against Tyler Robertson and Alex Burnett, the Twins loaded the bases with no outs in their final at-bat on two walks and Denard Span's single. Morneau then grounded into a double play against reliever Matt Thornton as a run scored and Plouffe grounded out to end the game.
"We had the right part of the lineup up there, the guys that are supposed to drive in the ball," Gardenhire said. "Morneau is going really well for us, and got some big hits for us, but you're facing a really good pitcher out there who throws really hard with a great angle. It was a good matchup, but [Thornton] got him today.
"But I like to see him up there, and even Trevor coming after. He's been swinging the bat pretty good, probably as well as anyone the past couple days. It was nice to see him out there, it just didn't work out."