Officials from the provincial government and railways did not immediately confirm whether hostages had been taken.
The train, which had been carrying about 400 passengers, was trapped inside a tunnel after the attack, in which it came under fire and the driver was wounded, police and railway officials said.
Security forces said an explosion had been heard around the tunnel and that they were exchanging fire with the militants in a mountainous area.
In a statement, the Baloch Liberation Army (BLA), a militant separatist group, said it had taken hostages from the train including security forces.
It threatened to execute the hostages if the security forces did not retreat.
The Jaffar Express had been on its way from Quetta in Pakistan's southwestern Balochistan province to Peshawar in Khyber Pakhtunkhwa when it was fired on, railway officials said.
The Balochistan province borders Iran and Afghanistan
Pakistan's interior minister Mohsin Naqvi condemned the attack and said the government would not make any concessions to "beasts who fire on innocent passengers".
The Balochistan government has imposed emergency measures to deal with the situation, officials said.
A decades-old insurgency in Balochistan by separatist militant groups has led to frequent attacks against the government, army and Chinese interests in the region, pressing demands for a share in mineral-rich resources.
The BLA seeks independence for Balochistan.
It is the biggest of several ethnic insurgent groups that have battled Pakistan's government for decades, saying it unfairly exploits Balochistan's rich gas and mineral resources.
with DPA
