The unidentified man was taken to hospital after bystanders doused the flames that enveloped him in the same spot at the elevated top of historic Wenceslas Square where Jan Palach set himself ablaze in January 1969.
Palach's suicide was a desperate act aimed at lifting the apathy hanging over the country in the wake of the Soviet intervention in August 1968 in which Soviet tanks and troops occupied Prague, snuffing out the Prague Spring process of democratic reforms to the Communist system.
"According to initial information, a man born in 1964 poured an inflammable liquid on his body and set himself on fire," Prague police said on their Twitter feed. An investigation was under way.
Paramedics put the man, who suffered burns over 30 percent of his body, into an induced coma before taking him to hospital, the Prague emergency service said.
There was no immediate word on the man's motives.