Reuters Italian media said a truck carrying cars collided on a bridge with another tanker truck containing inflammable materials.
Italian news agencies have reported that multiple injuries were caused by flying glass from broken windows.
Firefighters have extinguished the blaze and begun to investigate why it happened.
At least one person was killed and around 55 were injured, 14 seriously, according to local media. The explosion sent flames soaring into the air. Aerial photos showed a gaping hole in the highway next to the tanker. Dashcam footage and photos of the explosion have gone viral.
At least two people died and up to 70 were injured Monday when a truck exploded in Bologna, Italy.
Fire raging on the motorway outside Bologna
Witnesses and local reports suggest that a lorry carrying other cars was involved in the crash.
Italian prosecutors said the tanker was filled with liquefied petroleum gas, otherwise known as propane, used as a fuel in heaters, cooking equipment and vehicles.
- via Getty Images Firefighters work at the scene where the tanker truck exploded.
Authorities said a major highway interchange had been closed north of the city due to the accident. Video released by police shows an extensive crater and the charred remains of the destroyed truck.
Several people are believed to have been injured as well as two people dead.