The train was travelling from the coastal city of Port Elizabeth to Johannesburg when the crash occurred.
Video footage showed a fire blazing through at least one carriage, near an overturned truck and car. Evacuated passengers were seen standing on the roadside with luggage, the BBC reported.
The collision occurred near Kroonstad city in Free State province, after the truck failed to stop at a crossing, a passenger told local media.
About 850 passengers had been safely evacuated from the train, the police said.
The driver of the truck tried to flee, but was arrested by the police, passenger Seipati Moletsane told eCNA news site. Passengers in the first two coaches were wounded, she said.
"I was so traumatised. I was looking for a door just to jump out but every door was locked... All of a sudden, we saw smoke, smoke, smoke," Moletsane said.
Emergency assistance group Netcare911 said they were attending to the crash in the area of Kroonstad, a city 180 km south west of Johannesburg, along with other emergency services.
The number of dead could rise, authorities said.
(This story has not been edited by Social News XYZ staff and is auto-generated from a syndicated feed.)
