Some 30 people are being treated in hospital after they were trapped in their vehicles when the road caved in early on Wednesday morning.
State broadcaster CCTV reported a 17.9-metre (58.7-foot) stretch of the S12 highway between Meizhou city and Dabu county caved in at about 2:10am on Wednesday (18:10 GMT on Tuesday), trapping dozens of people in 18 vehicles.
As of 11:45am (03:45 GMT), “19 people have been confirmed dead, and 30 are receiving all-out emergency care in hospital”, CCTV reported.
It added that the lives of those in hospital were “not currently at risk” but did not go into detail on their injuries.
Social media footage shared by local news outlets showed flames and smoke rising from a deep, dark pit into which the cars appeared to have fallen.
Authorities have sent about 500 people to the site to help with the rescue operation, CCTV reported.
The cause of the collapse was not specified.
Guangdong has been hit by a series of extreme weather events in recent weeks, from heavy rain to flooding and a deadly tornado.