Emergency services were called to the house on Sefton Terrace at 12.11pm, after reports came in of the house collapsing.
An 18-year-old man is airlifted to Royal Preston Hospital with major trauma while a woman is being taken to Royal Blackburn Hospital for evaluation.
It is believed that the explosion affected other properties in the area. Emergency services advise members of the public to stay away.
A Northwest Ambulance Service spokesperson told LancsLive: “Two ambulances, an advance paramedic, air ambulance and an operational commander attended an incident after the 999 call at 12.11.
“We have taken two patients to the hospital. An 18-year-old man was taken to Royal Preston Hospital in great shock. A female patient was taken to Royal Blackburn. [Hospital] for evaluation.”
The Lancashire Fire and Rescue Service has released updates about the incident via Twitter.
He said: “We are currently dealing with an explosion at a home in Sefton Terrace, Burnley. One person was rescued by neighbors and taken to hospital.
Please avoid the area around Sefton Terrace and Piccadilly Rd.
She added: “We have three fire engines and an urban search and rescue team at the scene.
“We are working with other emergency services, local authorities and utility companies to make the landscape safe and to evaluate the property’s structure.
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“Firefighters at the scene are now using an aerial ladder to make the house structure safe by removing the coping stones from the gable end.”
Pictures from the scene showed emergency services closed off the area while firefighters used an aerial ladder to inspect the rooftop.
A Lancashire Police spokesperson said: “Please be advised that we are currently dealing with a house collapse in Burnley. We were called shortly this afternoon to Sefton Terrace. Emergency services including police, fire and ambulance are currently at the scene, and they have been evacuated.
“We are now asking people to avoid the area, particularly around Piccadilly Rd and Sefton Terrace, and are asking motorists to find alternative routes where possible.”
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Northern Railways has stated that due to the explosion near Burnley Manchester Road trains passing through that station, they will be canceled or delayed.
She said: “Due to a gas explosion near the railway, train services between Burnley Manchester Road and Todmorden/Hebden Bridge are not operating.
“Emergency response personnel have requested that all train traffic through the area be halted. Rail network personnel are on their way, and once they reach the site, we will be able to provide more information.”
Disruption was expected until 5:00 pm.