Between 30,000 and 100,000 people braved heavy rain for the protest, according to varying estimates from police and organisers.
Demonstrators chanted "No to Camorra" in reference to the Neapolitan mafia and some protestors carried photographs of relatives who they said had died from cancer.
The protest movement is calling for the decontamination of polluted land and water and blames the mafia for creating hundreds of illegal dumps in the area.
Locals call the zone between Naples and Caserta the "Land of Fires" or "Triangle of Death" due to the toxic fumes produced by burning waste.
Among the protesters were the mayor of Naples, environmental groups and local figures including the singer Nino d'Angelo and Father Maurizio Patriciello, one of the first to hit out against the problem.
Three tonnes of bread baked using ingredients from "clean" fields in the region were distributed to protesters.
The organisation Legambiente said that in 22 years some 440 businesses located in central and northern Italy have buried around 10 million tonnes of industrial waste in the area.