The Germany international made only his third La Liga start of 2014-15 in Saturday's 4-0 derby hammering against Atletico Madrid, but was substituted at half-time.
World Cup-winner Khedira has since been sent for a scan and the European champions on Monday confirmed that the 27-year-old is set for another spell on the sidelines.
A statement on the club's official website said: "Following the medical tests carried out on Sami Khedira by the Real Madrid doctors in the Sanitas La Moraleja Hospital, the player has been diagnosed with an injury to his left biceps femoris injury. His progress will be monitored."
Khedira has endured a frustrating campaign in which he has been troubled by injuries and overlooked by Carlo Ancelotti when fully fit.
The former Stuttgart man's contract expires at the end of the season and he continues to be linked with a move away from Santiago Bernabeu.
