Police, fire and ambulance crews were called to the Broadfield Lane Industrial Estate at about 1900 BST on Wednesday.
A Lincolnshire Police spokeswoman said she believed the explosion had been very quick and the men died instantly.
The sixth man has been taken to the Queen's Medical Centre in Nottingham.
Unconfirmed reports from local residents said they believed the men may have been migrant workers brewing illegal alcohol in the industrial unit.
Nerys McGarry from Lincolnshire Police said officers were at the scene and would remain at the unit overnight to carry out a forensic examination of the site.
Arm 'ablaze'She said it was not yet clear what had caused the blast.
Ms McGarry said she understood the explosion was a rapid blast as opposed to an "extensive fire" but could not give any further details.
"We do not have any further information about the men, their ages and where they are from but we will be making inquiries throughout the night and can give a further update in the morning," she said.
BBC Radio Lincolnshire reporter Scott Dalton, who was at the scene, said residents in the area had seen thick, black smoke coming from the industrial estate.
"Locals have been telling me they didn't even hear an explosion or even a bang," he said.
Paul Featherstone, who lives nearby resident, described what he had seen. "I heard the one fire engine come down, then a few more.
"I didn't hear an explosion, I just saw the smoke. If the explosion didn't kill them, the smoke would have done because it was that bad. It was thick, black smoke coming through the roller doors," said Mr Featherstone.
He added he was told by another eyewitness that one man ran out "with his arm all ablaze". It is understood this is the man who was taken to hospital in Nottingham. He remains in a serious condition.
Boston Central Councillor Peter Bedford described the news as a "real shock".
"There is heavy industry in that industrial estate, there's a scrapyard, there's joinery works, it's a real mix."
Boston East councillor Mike Gilbert said: "I'm very anxious to find out exactly what's happened. It's a lot of people dead and a great tragedy."
Broadfield Lane Industrial Estate is made up of about 10 units, including a furniture store, a scrap yard, a tyre place and a car maintenance business. The site is surrounded by houses and is close to Boston town centre.
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