Pakistan train accident: Dozens killed in Sindh collision.
Pakistan has seen a string of deadly train accidents over the past years.
The accident in Ghotki district happened early on Monday when the Millat Express coming from Karachi derailed, falling on to another track. It is not clear what caused the derailment.
A senior official in the Ghotki district, Usman Abdullah, told Reuters news agency it was hard to know how many people were still trapped in the train.
"There are about six to eight bogies [carriages] that are totally smashed... there is a sleeper train, AC [air conditioned] class, as well as economy class, in which there were between 47 to 50 people on this side and around 50 to 60 people on the other train," he said.
Prime Minister Imran Khan said he was "shocked" by the accident and promised a full inquiry.
Specialist equipment has been brought in to help to rescue those trapped in the tangled wreckage.
A passenger on board one of the trains told Agence France-Presse that he felt lucky to have survived.
"It happened at 03:30," he said. "We were asleep when we felt jerks. Luggage began to fall down. Thank God we stayed safe."
Hospitals in the area have been put on emergency alert to deal with the casualties, and helpline centres have been set up for passengers.