State broadcaster CCTV said a stretch of road between Meizhou city and Dabu county in Guangdong province caved in at around 2:10 am (1810 GMT Tuesday).
The incident caused 18 vehicles to become trapped and involved a total of 49 people, CCTV said.
As of 11:45 am, “19 people have been confirmed dead, and 30 are receiving all-out emergency care in hospital”, according to the broadcaster.
It added that the lives of those hospitalised were “not currently at risk” but did not specify their injuries.
Footage shared on social media showed a smoking pile of wrecked vehicles lying at the bottom of a deep muddy pit where the highway once ran.
Red fire engines and people in high-visibility vests congregated around a cordon erected a few metres from where the road had given way.
Other clips apparently filmed before dawn showed flames emanating from the pit.
“You can’t go any further,” a man is heard saying in one video, adding parts of the road had given way.
AFP was not immediately able to verify the videos.
Authorities have dispatched around 500 people to the site to help with the rescue operation, CCTV reported.
They are drawn from departments handling public security, emergency response, firefighting and mining rescue, according to the broadcaster.
Local authorities said in a notice that part of the S12 highway was closed in both directions and ordered drivers to take detours.
– String of disasters –
While the cause of Wednesday’s road collapse has not yet been specified, the incident is the latest in a string of deadly disasters to hit Guangdong in recent weeks.
The province — a densely populated industrial powerhouse — has been lashed by heavy rains that have caused deadly floods in some areas.
And a swirling tornado killed five people when it ripped through the megacity of Guangzhou last week.
Much of China’s massive highway network sprawls across rough terrain and extreme climates.
Road accidents are also common in the country due to a lack of strict safety controls.
In March, 14 people were killed and 37 others injured after a bus crashed inside an expressway tunnel in northern Shanxi province.
Sixteen died in a vehicle pile-up in central Hunan province in February last year, a month after 19 perished in an accident in eastern Jiangxi province.