Fillon, 63, has faced protests in recent weeks since he was charged over accusations he gave his wife a fake parliamentary job for which she was paid hundreds of thousands of euros.
The former prime minister was making his way to the stage in a hall in the eastern city of Strasbourg when a shaven-headed man in a T-shirt bearing the slogan "Students for Fillon" emptied a packet of flour on his face and down his suit.
Security guards wrestled the man to the floor and one of the guards tore off the T-shirt. From the podium, Fillon told the rally he was "the target of merciless persecution".
In 2012, A woman threw flour at front-running French presidential candidate Francois Hollande as he made a campaign stop Wednesday, in what she said was a protest against his Socialist Party.