The Belgian playmaker provided two assists at the Etihad Stadium as well as an excellent performance throughout the emphatic victory, which sees Stoke slip down to 15th points with eight points from as many games.
Despite the loss, Hughes was full of prase for De Bruyne and acknowledged that it was a difficult day for his side.
He told 'Sky Sports' after the game: "It was difficult from our point of view clearly. You don't want to concede the amount of goals we did although some of them were top class and with De Bruyne, you've got a genuine, world-class player in their ranks.
"We found it very difficult to stop his influence on the game and he was a big factor in them being able to take the game away from us.
"We got back into the game at 3-2, although if we're honest, I think it flattered us at 3-2 but very quickly, we made a few mistakes and they took the game away from us. In the end, we were grateful for the referee's whistle.
"You have to be right on top of your game and get the maximum out of your players in terms of performance levels. You need eights or nines across the board but unfortunately, we didn't get too many of them today."
Hughes was full of compliments for his former side Manchester City, but he said Stoke's season will not be defined by the negative result.
"They're a very accomplished side. They have power, pace, they anticipate situations very, very quickly and their guile and personality on the ball is as good as any," he added.
"We were better in the opening period of the second half, which we had to be because we were poor in the first half. We went up a gear and they went up three or four gears so that's the quality and capacity they've got.
"It's disappointing for us, we wanted to come here and do a lot better than we've been able to do but this won't be about stopping Man City. Our season will be defined by the types of teams we are going up against in the coming weeks."