Hughes, who has been the club's most consistent starter this year, left in the top of the fourth inning with a right shin contusion after being hit by a comebacker from Adam Dunn. The right-hander was charged with two runs on four hits over three-plus innings to get pegged with the loss, which dropped the Twins to 2-5 on their current 10-game homestand.
"It's tough," Hughes said. "We came off a road trip and played pretty well, and we thought we had a long homestand where we could turn things around a little bit, but obviously it hasn't been the case so far. But we have to keep plugging away.
"We traded a guy like Morales, who was a big addition when we got him, but that's the situation we're in. You have an opportunity to trade a guy for prospects and that's the way it goes. We have a responsibility to play better and not be in this situation."
The White Sox opened the scoring in the third with a two-out RBI single from Alexei Ramirez to score Adam Eaton, who doubled down the third-base line.
Dunn knocked Hughes out of the game the next inning on his hard-hit ball off Hughes' shin, which forced right-hander Samuel Deduno into the game. Hughes said he was fortunate he didn't break a bone on the play, but was still frustrated it forced him to leave the game early because he was pitching well at the time.
"Overall, my stuff was pretty good and I thought I could've thrown a pretty good game," said Hughes, who dropped to 10-7 with a 4.10 ERA in 21 starts. "But Noesi was really on today. It's the kind of thing you run into. But overall, I thought stuff-wise, it was a lot better than last time."
Deduno had trouble after Hughes departed, as he walked home a run with two outs -- with the run being charged to Hughes -- before giving up a two-run single to Eaton.
Deduno settled down after that and was able to get through four innings. He surrendered another run in the sixth on his own throwing error to third base. Deduno tried to throw out Gordon Beckham as he advanced to third on a grounder, but the throw sailed wide to allow Beckham to score easily.
"They got him for three runs, but then he settled in," Twins manager Ron Gardenhire said. "He was OK. It wasn't his best performance, but we desperately needed innings out there."
The offensive output was plenty for Noesi, who gave up two runs on just three hits and a walk over 7 2/3 strong frames.
"When you have command of your fastball, every pitch you can mix in and they're going to swing and miss," said Noesi, who struck out three and improved to 5-7 with a 4.99 ERA on the year. "But everything was working today."
The Twins didn't get a hit until the fourth inning on a two-out bloop single to left field from Trevor Plouffe that landed between three White Sox players.
Minnesota didn't get another hit until Chris Parmelee singled in the eighth and Danny Santana followed with a two-run homer with two outs. But it was all the Twins could muster against Noesi, and they went down quietly in the ninth against reliever Jake Petricka.
"We were trying to figure him out as the game went along, and Santana finally got one," Gardenhire said. "I think it was a mistake where he tried to go in but Santana was able to get the bat to it. But other than that, he was fantastic. He pitched great."