Ryan Shawcross has been ruled out for up to three weeks with a problem with a disc in his back.
But without skipper Shawcross, Hughes has faith in Phillip Wollscheid and Marc Muniesa, who were the centre-back partnership when the Potters took three points from the King Power Stadium against Leicester.
Hughes told his press conference: “Unfortunately Ryan will be missing now for a couple of weeks.
“That is a big disappointment for us because he is obviously an important player for us and the captain, so he will be a miss.”
The Welshman added that last weekend’s hat-trick hero Jonathan Walters is also a doubt for the trip to Tyneside, to play in front of the Sky cameras, as he hasn’t trained this week.
Stoke have painful memories of this fixture last year after Martin Atkinson sent-off Glenn Whelan and Marc Wilson before awarding Newcastle two penalties in the 5-1 thrashing.
Hughes said: It’s never easy going to Newcastle, as we found out last year. We hope the referee doesn’t play a part as he seemed to do last year.”
Newcastle recorded their first victory under permanent boss John Carver against last weekend.
He will be able to recall Paul Dummett who has recovered from injury, but Dutch forward Siem de Jong is not quite ready despite playing his second comeback game during the week.
The game will mark as Mike Williamson’s fifth year at the club where he has featured 155 times since joining in 2010.
One alarming statistic for this fixture is that the home side has won all of the last six meetings.
The match referee is Chris Foy. He has refereed Stoke once this season and saw the Potters throw away a two-goal lead against West Ham United, while he oversaw the Magpies 1-0 home victory over QPR and their 4-0 defeat at Southampton.
The Merseyside official has handed out 64 yellow cards and eight red cards. He will be assisted by Mike Mullarkey and Ian Hussin.