The train was transporting 26 tanks of propane-butaine in the Hitrino village of the Shumen Province in the east of the country. Their explosion was lethal.
"At least four people died and over 20 were injured," a local fire-fighting crew's chief Nikolay Nikolov said as quoted by the BTV.
The injured individuals have been hospitalized. Medics and firefighters are working at the site. The village was cordoned off by police.
The head of a hospital in the city of Shuman said 23 people have been hospitalized, most of them with multiple burns.
Bulgaria's acting prime minister Boiko Borisov headed to the scene.