Keira Walsh suffered a suspected anterior cruciate ligament injury in England's World Cup clash with Denmark on Thursday.
The midfielder slid in to make an interception but appeared to catch her studs in the ground and she stayed down in agony.
As medics rushed onto the pitch, Walsh mouthed 'I've done my knee', and she is now almost certain to miss the rest of the tournament.
It is a severe blow to England's hopes, with Walsh having been the heartbeat of the team under manager Sarina Wiegman.
Her misfortune comes after captain Leah Williamson was ruled out of this summer's tournament with the same injury, while Beth Mead failed to recover in time from her own ACL setback.