PSV full-back Willems was substituted in the 42nd minute of his side's 2-0 home defeat to Feyenoord with what is described as "damage to the inner tube of his knee."
The 20-year-old has won 11 caps for Netherlands in his international career, his most recent coming in the 2-2 draw with Japan in November last year.
But his prospects of earning a place in Louis van Gaal's squad for the World Cup in Brazil are now in question after interim PSV boss Ernest Faber - in charge while Phillip Cocu recovers from surgery on a tumour in his back - admitted the injury is a bad one.
"Willems has suffered an injury to the inner tube," Faber said in quotes reported by De Telegraaf. "It does not look good."
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