Police closed the highway and the surrounding area of Borgo Panigale.
Italian news agency ANSA said the tanker was transporting flammable substances and exploded on impact.
Dramatic footage shared on social media shows a huge fireball in the sky and smoke rising over the landscape at Bologna airport in the country's north.
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Reuters Scores of people have been injured in the blast.
Firefighters are now battling the flames at the scene on the bypass in Borgo Panigale, according to local reports.
In a tweet, Bologna Airport said it wasn't affected by the explosion.
Italian media reports that some people were injured by glass flying from windows shattered by the force of the explosion.
In a separate incident on Monday, 12 migrant labourers died in the southern Italian region of Puglia when the van they were travelling in smashed into a lorry.