The second-seeded Medvedev emerged with a 7-6 (3), 6-3 win in Beijing, but not before his 12th-ranked Australian opponent had staged a comeback from trailing 5-2 in the first set to force a tiebreaker.
"It's crazy how every time he is down in a match, you know he is going to start playing like he is No. 1 in the world," Medvedev said. "Tough to play against him, a tough victory, but I am happy with my level.
"Confidence is key. When I am in good shape and good form, I have this ability to win these kinds of matches in straight sets. If I'm missing just 2% of what I'm doing right now, that's when it's tougher."
Humbert thwarted Rublev's attempt to serve out the match at 5-3 in the final set and then completed the comeback victory with a dominant tiebreaker.