The China Eastern Airlines Boeing 737 was flying from Kunming to Guangzhou when it came down in Guangxi province and caught fire.
It is feared there are no survivors, but the number of casualties and reason for the crash are not yet known.
Chinese airlines generally have a good safety record: the last major accident took place 12 years ago.
Flight tracking data suggested the plane lost height rapidly from its cruising altitude before hitting the ground.
More than 600 emergency responders are said to be at the crash site. Firefighters reached the scene first and managed to extinguish a blaze in the hills caused by the crash.
Footage taken by local villagers and shared on Chinese social media - and by state broadcasters - showed fire and smoke from the crash, and plane debris on the ground.