The force of the explosion caused two of the train cars to overturn and catch fire, sending thick black smoke into the air, according to footage shared online, AP reported.
The attack happened in an area where security forces are usually stationed, badly damaging several nearby buildings and smashing vehicles parked along the road, according to witnesses and images circulating on social media.
Doctors at local hospitals said they had received more than 30 wounded people, several of them in critical condition.
Baluchistan government official Babar Yousafzai said authorities were still investigating the blast, but gave no further details.
Quetta is the capital of insurgency-hit Baluchistan province.
The oil- and mineral-rich province has long been the scene of a low-level insurgency, with separatist groups such as the outlawed Baloch Liberation Army demanding independence from Pakistan’s central government. The insurgents have frequently targeted security forces, government installations and civilians in the province and elsewhere in the country.
No one immediately claimed responsibility for the attack.