Hughes, England’s first choice at number eight in the continued absence of the injured Billy Vunipola, has bone bruising in his right knee joint.
As a result, he has returned to his club, Wasps, and is set to require three to four weeks of treatment.
Watson impressed at full-back in England’s win over Australia last weekend, but will not feature against Samoa on Saturday with Mike Brown available again. Brown missed the Australia game after suffering a nasty blow to the head in the previous week’s match against Argentina.
Bath flanker Sam Underhill will continue to go through his return-to-play protocols in camp after he was substituted early against Australia due to a head knock.
After beating Argentina and Australia, England will be expected to record another victory in their final match of 2017.
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