Huget sustained the injury to his right knee ligaments in his team's Pool D opener, a 32-10 win over Italy on Saturday at Twickenham,
"It is sad to lose such a player. We don't know yet whether his ligament is totally or partially ruptured, but his World Cup is over," coach Philippe Saint-Andre said on Sunday.
Huget is being replaced by powerful Castres Olympique wing Remy Grosso.
The 28-year-old Huget, who has 41 caps, has been a key member of the French squad since Saint-Andre took over from Marc Lievremont after the 2011 World Cup.
Four years ago, Huget withdrew from the World Cup squad after failing to provide his whereabouts to anti-doping authorities on three occasions.
France next face Romania and Canada at the World Cup, before concluding their group campaign against Ireland.
(Reporting by Julien Pretot; Editing by Ed Osmond/Mitch Phillips)
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