It happened around 4 a.m. at Lee's Deli at the intersection of 47th Street and Baltimore Avenue.
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According to police, the U-Haul driver hit the main support beam of the deli, which forced a brief evacuation of the two apartments above the business.
One woman who lives above the deli tells Action News she thought the impact of the crash was an explosion.
Throughout the day people came to see the popular corner store now boarded up. The owners say they will reopen after Thanksgiving.
"It's one of the consistently most busy businesses in this neighborhood," said Nicholas Baptiste of West Philadelphia. "(It's) very strange sight seeing it all boarded up."
"I'd certainly be willing to pitch in if they need it. But they do a lot for the neighborhood, hope we can have Lee's again soon," added Jessie Litvin of West Philadelphia.
The owner of the deli, Scott Lee, thanked the community for the support.
As staple in West Philadelphia for 30 years, Lee says while the last few years have been tough for every small business, there is a lot to be thankful for this season.
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No injuries were reported in the crash.
Police are still investigating what caused the driver to hit the building.
Neighbors say they did see the driver leave the scene with police. There was no immediate word on if any charges were filed.