Guangdong, a densely populated industrial powerhouse, has been lashed by rainstorms in recent weeks, causing severe flooding and landslides in some areas.
The downpours have been much heavier than would normally be expected for the time of year and have been linked to accelerating climate change.
State news agency Xinhua said that a stretch of road between Meizhou city and Dabu county in Guangdong province caved in at around 2:10 am on Wednesday (1810 GMT Tuesday).
The incident caused 20 vehicles to become trapped and involved a total of 54 people, according to Xinhua.
As of 3:00 pm (1900 GMT), "24 people have been confirmed dead, and 30 are receiving all-out emergency care in hospital", Xinhua said.
Recovery work was ongoing and the lives of those hospitalised were "not currently at risk", it added, without specifying their injuries.
An aerial photograph published by state broadcaster CCTV showed wrecked vehicles lying in a deep muddy pit where the highway once ran.
Dozens of emergency vehicles and cranes congregated along the intact section of the road, which bisects a steep, wooded slope.
Videos circulating on social media -- apparently filmed before dawn -- showed flames and smoke emanating from the pit.
"You can't go any further," a man is heard saying in one video, adding that parts of the road had given way.
AFP was not immediately able to verify the videos.
CCTV said the collapse was a "natural geological disaster... (that occurred) under the impact of persistent heavy rain."
It reported that a nearly 18-metre (59-foot) stretch of road had fallen away.
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 -
The incident is the latest in a string of disasters attributed to extreme weather events in Guangdong in recent weeks.
Massive downpours last month sparked floods in a different part of the province that claimed the lives of four people and forced the evacuation of over 100,000.
And a swirling tornado killed five people when it ripped through the megacity of Guangzhou last week.
Parts of the province have not seen such severe flooding so early in the year since records began in 1954, according to state media.
"Intensifying climate change" had raised the likelihood of the kind of heavy rains not typically seen until the summer months, Yin Zhijie, the chief hydrology forecaster at the Ministry of Water Resources, told state-run China National Radio last month.
China is the biggest emitter of the greenhouse gases that contribute to climate change but has pledged to reduce emissions to net zero by 2060.
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