"The player Ever Banega has suffered an accident with his own car after training on Sunday when he received a trauma to his left leg that caused a fracture to his tibia and the perone bones," Valencia said in a statement.
The club said the break had not been clean, the area was inflamed, and after hospital checks that surgery would take place on Monday.
"The period of recovery is estimated to be around six months," the statement added.
The Argentina international, 23, had already been left out of the Valencia squad to visit Barcelona in La Liga on Sunday as he was struggling with a knee problem.
Valencia lie third in the standings and play Stoke City in a Europa League last-32 second leg next Thursday.