A house has collapsed sparking the evacuation of several properties as two people - including a teenager - have been rushed to hospital.
An 18-year-old man was airlifted to Royal Preston Hospital "suffering major trauma" and a woman was also taken to the Royal Blackburn for assessment, authorities said.
Burnley Police, Lancashire Fire and Rescue and North West Ambulance Service are at the scene on Sefton Terrace.
Two people were rescued by neighbours, the fire department said.
It is unclear what caused the explosion.
This is a mostly residential area a short distance from Burnley Manchester Road train station.
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A Lancashire Fire and Rescue spokesperson 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.
"We have three fire engines and our urban search and rescue team at the scene.
"We're working with the other emergency services, local authorities and utility companies to make the scene safe and assess the structure of the property.
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"Please avoid the area around Sefton Terrace and Piccadilly Road."
A spokesperson for the North West Ambulance Service said: "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 the hospital.
"A male patient has been airlifted to Royal Preston Hospital suffering major trauma.
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"A female patient was taken to the Royal Blackburn for assessment."
Burnley Police tweeted: "Please be aware we are currently dealing with a house collapse on Sefton Terrace, in #Burnley.
"Emergency services are at the scene and several properties have been evacuated.
"We are asking people to avoid the area around Piccadilly Road and Sefton Terrace. Many thanks."
Police later tweeted that roads had reopened but authorities remained at the scene.