Defoe sustained the injury midway through the second half of England's win over Switzerland on Tuesday night.
The injury is set to sideline Defoe for six weeks at least and means he will miss several of Spurs' Champions League group games, starting next week's trip to Werder Bremen.
"Even if it's a bad sprain, you're still talking about six weeks or so, because it's a nasty one," said Spurs boss Harry Redknapp.
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