Emergency services rushed to the scene following the blast, which took place shortly after 2 pm.
According to La Repubblica, the explosion was loud enough to be heard in several parts of Livorno.
The area around the tank was evacuated and teams of firefighters were on hand, though no fire was reported. The area was secured within a couple of hours.
Photos from the scene show the tank keeling over after the blast.
Mi sto precipitando a #Livorno da #Firenze, viste le tragiche notizie che arrivano dal porto, dove una violenta esplosione ha distrutto una cisterna e provocato, pare, morti e feriti pic.twitter.com/dFg89gRIYi— Filippo Nogarin (@nogarin) March 28, 2018
An image shared by the mayor of Livorno, Filippo Nogarin, who visited the port after the blast.
The shore tank, which was located in the Neri industrial depot specialized in the storage of liquids, is said to have contained the flammable substance ethyl acetate.
The two men killed are believed to have been carrying out maintenance near the unit, which had reportedly been emptied.
According to reports, they were employees of local environmental services company Labromare, one aged 52 and the other 25.
One victim died instantly, while the other was still alive when emergency services arrived but could not be resuscitated, Repubblica said.
The Neri depot is north of the passenger terminal where cruise ships dock. Image: Google Maps
The mayor of Livorno, Filippo Nogarin, visited the port hours after the incident, which he called an "immense tragedy".
"How much longer does the list of victims and workplace tragedies need to get before we manage to do something," he said, calling for a full investigation into the explosion.
Prime Minister Paolo Gentiloni also expressed his condolences to the families of those killed and his solidarity with Livorno, Nogarin said.