Riina, aged eighty-seven, former boss of the feared Cosa Nostra, was jailed in 1993.
He was serving twenty-six life sentences and is believed to have ordered more than one hundred and fifty murders.
Riina had been in a medically induced coma and his family had been given special permission to visit him in the prisoners’ wing of the hospital in Parma.
The mobster’s eldest son, Giovanni, is serving a life sentence in jail.
Riina was behind a series of mafia bombings in Rome, Milan and Florence in 1993, which left ten people dead.