Six fire engines were involved in tackling the blaze at Tooley Road at about 12.30pm.
Police say it is believed the victim was a man in his 30s, although formal identification has not yet taken place.
Lincolnshire Fire Brigade say they were called to a domestic property at 12.17 on Monday afternoon.
Crews from Boston, Spalding, Horncastle and Doningon attended the fire, with six appliances on scene to extinguish it.
Fire and police investigations into the cause have begun and are ongoing, the fire service said.
A spokesperson for Lincolnshire Police said: “Our officers attended the incident following a report from the fire service at around 12.30pm on Monday 10th May.
“The person who has died is believed to be a man in his 30s. Formal identification has not yet taken place.
“Police and Fire and Rescue are carrying out investigations to establish the cause of the fire. We will release an update when we have one available.”