Tottenham have confirmed England captain Harry Kane has sustained a "significant lateral ligament injury to his left ankle".
The 25-year-old striker suffered the injury in the 1-0 win over Manchester City in the Champions League quarter-final first leg on Tuesday.
Kane's injury could rule him out for the rest of the 2018-19 season, according to BBC.
Spurs have also said England midfielder Dele Alli, 23, fractured his left hand during the same match.
A club statement said Alli will be assessed before Saturday's home Premier League match against Huddersfield Town.
Kane, who has scored 24 goals for Tottenham this season, had slipped as he tried to block City full-back Fabian Delph's clearance on the right touchline in the second half and was substituted immediately.
After Tuesday's match, Spurs manager Mauricio Pochettino said: "It's a worry for us.
"We are going to miss him - maybe for the rest of the season. We hope it is not a big issue but there is not too much time to recover."
Tottenham are fourth in the Premier League with six matches remaining, two points behind third-placed Chelsea - who have played a game more - and one point ahead of north London rivals Arsenal, who are fifth in fifth.
The second leg of their Champions League tie against City is on Wednesday, 17 April at Etihad Stadium.
Kane has scored 22 goals in 37 appearances for England, who face the Netherlands in the semi-finals of the Nations League on 6 June.
The winners of that fixture will play either Portugal or Switzerland in the tournament's final three days later.
Kane has missed 21 club games since the start of the 2016-17 season with ankle injuries alone.
He was ruled out for almost two months in January, missing seven games, when he damaged ligaments in the same ankle during their 1-0 Premier League home defeat by Manchester United.
He also missed a month of last season with a similar injury to the right ankle, and endured separate absences of six and four weeks during the 2016-17 campaign.