Santa Cruz has been struggling with injuries since joining City from Blackburn in the summer.
The Paraguayan ace made his first start for the club against Scunthorpe and marked it with a goal in the 5-1 win.
Santa Cruz has been out with tonsillitis over the past week.
“He was really ill over the weekend and we had been looking to get him involved at the weekend on the bench, but he just couldn’t make it,” Hughes told Sky Sports.
“I was really pleased for him. It’s important whenever a striker comes to a club that he gets off the mark and I thought his all-round game was excellent.
“I know the quality he has and I was pleased today that he has been able to demonstrate that to everyone in the stadium, and he’s going to be a really important player for us as the season progresses.”
