Eighth-ranked Medvedev defeated French qualifier Pierre-Hugues Herbert 6-2, 6-4 in a repeat of the 2021 final, which Medvedev also won.
Medvedev, playing in Marseille on a wild card after second-round exits at the Australian Open and in Rotterdam, is seeking his first title since Rome in 2023.
He will next play Germany's Jan-Lennard Struff, who beat Frenchman Hugo Grenier 6-4, 5-7, 6-4, for a place in the semi-finals.
Zhang belied his ranking of 52 to stun Hurkacz 6-4, 6-7(1), 6-3 in a big-hitting battle in which he cracked 37 winners to the Pole's 30 during their two-hour, eight-minute clash.
"I felt great on court today, it was the same goal as the first match, I tried to put the match to the tie-break, and that's how I wanted to play," said Zhang, who reached the quarter-finals in Marseille in 2024.
"I guess I like it here, two years in the quarters."
Zhang next faces Belgium's Zizou Bergs who defeated Portugal's Nuno Borges 6-2, 6-7(5), 6-2.