Emergency services were called to the house in Sefton Terrace at 12.11pm, following reports the house had collapsed.
An 18-year-old man was airlifted to Royal Preston Hospital suffering major trauma while a woman was taken to Royal Blackburn hospital for assessment.
The explosion is believed to have affected other properties in the area. Emergency services are advising members of the public to stay away.
A spokesperson for North West Ambulance service told LancsLive: “Two ambulances, an advanced paramedic, an air ambulance and an operational commander attended an incident following a 999 call at 12.11.
“We’ve conveyed two patients to hospital. An 18-year-old man has been airlifted to Royal Preston Hospital suffering major trauma. A female patient was taken to the Royal Blackburn [Hospital] for assessment.”
Lancashire Fire and Rescue Service issued updates about the incident via Twitter.
It said: “We’re currently dealing with an explosion in a house on Sefton Terrace, Burnley. One person has been rescued by neighbours and taken to hospital.
“Please avoid the area around Sefton Terrace and Piccadilly Road.”
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Pictures from the scene showed that emergency services had closed the area while firefighters used an aerial ladder to inspect the roof.
A spokesperson for Lancashire Constabulary said: “Please be aware we are currently dealing with a house collapse in Burnley. We were called shortly after midday to Sefton Terrace. Emergency services including police, fire and ambulance are currently at the scene and several properties have been evacuated.
“We are now asking people to avoid the area, especially around Piccadilly Road and Sefton Terrace, and for motorists to find alternatives routes where possible.”