The Fire Service (NIFRS) is at the blaze is at O’Doherty’s on Railway Street.
West Tyrone SDLP MLA Daniel McCrossan was nearby when he heard an “explosion” and said there had been a “very loud lightning strike in the wider area”.
There were thunderstorms in the area at the time, but the cause of the fire has not been confirmed.
NIFRS said it received a call a shortly after 4 pm.
There are 80 firefighters currently at the scene, with 10 fire engines and further special appliances.
“We are currently dealing with a large commercial building on fire,” a fire service spokesman said.
The operation is expected to continue on Monday, with the public asked to stay out of the area due to the high level of activity.
Speaking to BBC News NI, Mr McCrossan, who owns a pub near to where the fire is, said there were about 20 firefighters at the scene.
“It is quite a significant blaze, the building that is struck is O’Doherty’s coffin makers,” he said.
“Luckily no one is hurt. There is a house next door, thankfully they weren’t home and they weren’t hurt either.”
He said the firefighters at the scene are working to contain it from spreading to other businesses, which have been evacuated.
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