Jose Ramon Sandoval will lead Granada until the end of the season following the departure of Abel Resino.
The Liga strugglers, who have four matches left to play, appointed Resino to take over from Joaquin Caparros as head coach on January 19.
Caparros paid the price for a run of 15 without a win that left Granada bottom of the league.
But results failed to pick up at Estadio Nuevo Los Carmenes as Resino tasted victory only twice.
Thursday's 2-1 defeat to Espanyol means Granada sit 19th, six points from safety.
Sandoval has previous experience of coaching in the top flight, having guided Rayo Vallecano to promotion from the second tier in 2011.
The 46-year-old, who celebrates his birthday on Saturday, subsequently returned to the Segunda in 2012 with Sporting Gijon but was relieved of his duties two years later.
Granada are on an eight-match winless slump and travel to Getafe in La Liga on Sunday.
