Most of the dead were passengers on the train, which derailed, the transport ministry said. Both drivers were also killed.
The interior ministry said the train was heading into the capital from the town of Gaafour, 120 kilometers (80 miles) to the southwest, in the morning rush hour.
The collision happened near El Fahes, some 60 kilometers from Tunis, at around 6:30 am (local time).
"The death toll could rise," Transport Minister Mahmoud Ben Romdhane told Mosaique FM radio.