Most of the dead were passengers on the train, which derailed, the transport ministry said.
The accident happened at El Fahes, some 60km from Tunis, at around 6:30am (05:30 GMT) in the midst of the morning rush hour.
The interior ministry said the train was heading to the capital from the town of Gaafour, 120 kilometres to Tunis' southwest.
"The death toll could rise," Transport Minister Mahmoud Ben Romdhane told Mosaique FM radio.
Witnesses spoke of mangled wreckage at the scene and dead bodies strewn across the tracks, according to AFP news agency.
"This is horrible, there is blood and bits of flesh everywhere," one witness told Shems-FM radio. "There are people still trapped under the carriage, which overturned."
Those injured in the collision were taken to hospitals in El Fahes and Zaghouan, and the scene of the accident was visited by the ministers of interior and health.
Train crashes are common in Tunisia, which has a dilapidated rail network featuring many unprotected crossings.
In July, a train derailed in the country's northwest, killing five people and injuring around 40.