Santa Cruz has been hampered by injury since his move from Blackburn Rovers in the summer and he had been restricted to three substitute appearances prior to Wednesday's Carling Cup fourth round tie.
However, Santa Cruz marked his first start for the club with his first goal as he headed City back in front in the first half before Hughes' side ran out convincing 5-1 winners.
And though Hughes has a wealth of options up front this season, the City boss is predicting Paraguayan ace Santa Cruz, who had been suffering from tonsillitis over the past week, will be a key player.
Excellent"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."
Second-half goals from Joleon Lescott, Carlos Tevez and Michael Johnson eventually put Scunthorpe to the sword after the Championship side had drawn level in the first half following Stephen Ireland's early opener for the hosts.
Hughes said: "I think it's important to get the game out of the way and credit to Scunthorpe, they played some good stuff at times.
"That was a bit of a consequence of the way we approached the first half as we gave them too much time and space, but the second half was much more like what I wanted.
"We had more intensity and were a lot more dynamic and, as a consequence, we ran away with the game."
City are now in the quarter-finals and Hughes believes the club are in with a chance of lifting a major piece of silverware for the first time in over 30 years.
"There are a number of big teams still left in the competition and a number of them are focusing on this competition this year," continued the Welshman.
"Sometimes some of the big clubs view it as an irrelevance, but I don't think that's the case this year.
"They would like to win this trophy, as we would ourselves."