The former Italy boss leaves with the club outside La Liga's relegation zone on goal difference.
Voro, who has previously been caretaker-boss four times, is in charge again, although it is not clear if it is on a long-term basis.
Gary Neville was sacked in March after four months and replaced by Pako Ayestaran, who was then fired in September, and replaced by Prandelli.
Valencia have spent one season outside La Liga since 1931.
Valencia boss Cesare Prandelli has resigned after 10 games in charge.