The striker had to be withdrawn early on in the 6-0 FA Cup victory at White Hart Lane after seeming to twist his ankle, and it could mean the end of his season as the club await the swelling to decrease before conducting tests.
"Harry is our main striker, one of the best in England, but we can't cry about it now," said Spurs manager Mauricio Pochettino.
Despite losing their top scorer, Spurs still cruised into the semi-finals thanks to a hat-trick from Son Heung-Min, his first for the club.
"We have to be positive. We have enough players to try and replace him. It won't be excuse if we don't win or achieve our aims because Harry is not in the team," Pochettino added.
While the South Korean stole the show against the Lions, it was also a big evening for Vincent Janssen, who came on as a substitute to score his first goal from open play since joining from Feyenoord.
The Dutch striker has underwhelmed since coming over from the Eredivisie, but this could be his chance to carve out a place in the team in the absence of the striker.