Midfielder Alejandro Faurlin faces six to nine months on the sidelines after suffering a third cruciate ligament injury in as many seasons.
The 28-year-old Argentine landed on his left knee during Wednesday's 1-0 Capital One Cup loss at Burton Albion.
"We're all desperately saddened and disappointed for Ale," said QPR manager Harry Redknapp
Faurlin had signed a new one-year deal in July after spending time on loan at Italian club Palermo.
"He is a great man and player, and he's suffered terribly bad luck over the last few years with injuries," added Redknapp.
Faurlin suffered an injury to his right knee in January 2012, and to his left knee in November 2013.
QPR say Wednesday's incident appeared innocuous but a scan revealed he had a new injury.
Signed from Argentine side Instituto in 2009, Faurlin has made 130 appearances for Rangers.
He was voted the club's player of the year in his first season at Loftus Road and had a key role in their promotion to the Premier League in 2011.