The 35-year-old winger, who is out of contract in the summer, could have played his last match for the Cottagers, while Felix Magath is still confident the Cottagers can stay up
The veteran midfielder - who turned 35 last Sunday - is out of contract in June and looks set to take no further part in the club's battle to remain in the Premier League.
Duff has made 173 appearances for Fulham since joining from Newcastle in 2009, the most he has played for one club during a career that also included spells at Blackburn and Chelsea.
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"The problem is his knee - an injury from three weeks ago which he had before I arrived here - and maybe he needs an operation."
The Cottagers sit at the foot of the table but have the chance to leapfrog Cardiff City should they win Saturday's encounter against the Bluebirds and, ahead of a crucial juncture in Fulham's season, Magath has backed his players to stay up.
"I'm convinced that we will avoid relegation because we have developed in the last 14 days (since he took charge) and the team is growing together and that is what makes me sure," the German continued.
"We have a quite good schedule in the last 10 games.
"I get the feeling here that everybody knows that everybody sleeps well with this knowledge that are games ahead of us that we can win."