The Emergency Services confirmed that the Shosholoza Meyl Train 37012 was traveling from Port Elizabeth to Johannesburg, when it hit a truck at Jeneva level crossing between Henneman and Kroonstad in Free State province.
Transport Minister Joe Maswanganyi said the derailment left 18 people burned to death and 239 injured.
Firefighters and medical personnel have rushed to the scene to help the victims.
Footages sent by passengers from the scene shows a number of carriages laid on the ground and engulfed in flames.