Four fire engines from Preston, Penwortham, Bamber Bridge, and Hyndburn, together with an aerial ladder platform from Hyndburn, attended at 19:52pm.
The incident involved the ground and first floor of a domestic property, with firefighters using six breathing apparatus and two hose reels to extinguish the fire.
Four casualties received treatment from firefighters and North West Ambulance Service paramedics before being conveyed to the hospital by ambulance.
Lancashire Police say that three people – a woman aged in her 20s and two children aged three and five – have been taken to hospital in a critical condition.
Their next of kin have been informed and are being supported by specially trained officers.
The fire had been extinguished by 20:47 pm last night and police say the incident is currently being treated as unexplained.
A cordon is in place around the address and police are asking people to avoid the area if possible.
Anybody with information is asked to call 101, quoting log 1305 of April 8th.