Stoke slipped to a fifth defeat in six Premier League games on Wednesday, thanks to Adam Johnson's tap-in in the 17th minute at the Stadium of Light.
The visitors had opportunities to level with Ryan Shawcross seeing Vito Mannone pull of a superb stop from point-blank range shortly before half-time, while the centre-back hit the crossbar in the closing stages.
But Hughes was incensed that N'Zonzi was shown a second yellow card and subsequent red in the 52nd minute, with referee Robert Madley deeming the midfielder had tugged Jozy Altidore to ground when the striker had broken free of the defence, after receiving his first caution for hauling down the American in the first half.
"It was a performance of real character and desire," said Hughes. "Unfortunately on too many occasions this season we've been hurt by refereeing decisions that have impacted upon the game.
"Once again we're talking about a situation that I feel was a poor decision by the referee. It's difficult for him, the lad Altidore has gone down easily looking for an advantage. I felt on the night too much of that was going on to be perfectly honestly.
"The referee has to be able to look through that and understand what's happening but he's bought a challenge where there's very minimal contact.
"The lads gone down easy, the referee deemed it necessary to give Steven a second yellow for that challenge which is unbelievable in my opinion."
With the January transfer window due to shut on Friday, Hughes confessed it is unlikely he will add to his squad, despite fresh links with Sunderland's Lee Cattermole, who took no part in the game.
"I haven't had an update because I've been at the game," he added. "At the moment the possibility of getting more in isn't high I would suggest.
"But we'll see things happen quickly in the window. If we don't get anyone else in so be it. The group I've got showed they're an excellent group."
