Underhill’s club Bath have confirmed the 22-year-old will be out of action for up to three months.
Underhill suffered damaged ankle ligaments during Bath’s victory against Leicester on December 30.
It was initially thought Underhill had merely rolled his ankle but after seeing a specialist it was decided he needed an operation, ruling him out until mid-April.
The news comes as a blow to England head coach Eddie Jones following Underhill’s impressive displays in the Autumn internationals.
England kick off their Six Nations campaign against Ireland in Dublin on Saturday, February 2.
Their final match is against Scotland at Twickenham on Saturday, March 16.
Bath also announced flanker Tom Ellis faces eight weeks out with an elbow injury.