The forward suffered the injury in a challenge with Wolves midfielder Karl Henry after 27 minutes and left the pitch on a stretcher after receiving oxygen.
"He has broken his leg just above the ankle," Hughes told the BBC.
"He will have an operation tomorrow. He's out for a minimum of four months but if it's worse it could be longer. It's a big loss."
The injury is a huge personal blow of Zamora who missed out on a possible place in England's World Cup finals squad after needing surgery on an Achilles injury that dogged him in the last few weeks of last season.
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