Huth came off in the second half of Saturday's 2-0 Barclays Premier League win over Sunderland at the Britannia Stadium.
And giving an update on the German centre-half's condition on Friday, Hughes said: "Unfortunately Robert Huth has got a problem with his knee.
"We hoped that we would be able to manage him through it to be perfectly honest, but it looks like he will have to have an operation on it, so we are going to lose him for a number of weeks."
Hughes, who was speaking at his pre-match press conference ahead of Saturday's top-flight trip to Everton, will also be without forward Marko Arnautovic for the game.
Hughes said: "Marko pulled up with a hamstring strain, so he is out as well.
"We hope to get him back sooner rather than later, but he will be missing."