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Heavy rains caused a stretch of road running from Meizhou city towards Dabu county to cave in at around 2:10 a.m. on Wednesday (1810 GMT Tuesday), according to state news agency Xinhua.
Vehicles careened into the nearly 18-metre-long (59-foot) gash in the tarmac and plummeted down the steep slope below.
Guangdong, a densely populated industrial powerhouse, has been hit by a string of disasters attributed to extreme weather events in recent weeks.
The storms have been much heavier than expected this time of year and have been linked to climate change.
The highway collapse trapped over 20 vehicles and involved 54 people, according to Xinhua.
"As of 5:30 a.m. on (Thursday)... 36 people have died, and 30 people have been injured," Xinhua said, adding that the injuries were not life-threatening.
The death toll was up from 24 people on Wednesday afternoon.
Footage by state broadcaster CCTV on Tuesday showed excavators digging through the muddy hillside below the collapsed road.
Nearby, a crane lifted charred, wrecked vehicles onto a lorry as people watched from behind a cordon.
State media called the road collapse a "natural geological disaster" caused by the "impact of persistent heavy rain".
Around 500 people have been dispatched to help with the rescue operation, CCTV said Wednesday.
The provincial government has "mobilized elite specialized forces and gone all out to carry out... search and rescue", according to Xinhua.
An official notice on Wednesday advised that part of the S12 highway was closed in both directions, requiring detours.
A highway collapse is seen in Guangdong, China. Video courtesy of X/Zheng850349
More disasters likely
Last month, massive downpours in a different part of the province sparked floods that claimed four lives and forced the evacuation of over 100,000 people.
And a tornado killed five people when it ripped through the megacity of Guangzhou last week.
With rainfall expected to intensify throughout May, the government has warned of possible further disasters.
"Multiparty discussions and evaluations indicate that strong convection and heavy precipitation may increase in China in May," Xinhua cited the emergency management ministry as saying.
The country's lush southern and southeastern provinces -- including Guangdong -- are likely to be among the worst hit, leading to "a higher risk of geological disasters", the ministry was quoted as saying.
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.
