Calls came in around 9 a.m. for a report of a man with a knife at the CW Hotel in the 900 block of Folsom Street.
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Police say officers made contact with the suspect and at least one of them fired their weapon.
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"Officers immediately rendered aid and summoned medics to the scene for the suspect who was injured," said San Francisco Police Department spokesperson Robert Rueca.
The suspect was taken to Zuckerberg San Francisco General Hospital, where he later died.
Some residents of the building were shocked by the day's events.
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San Francsico, other police departments in war of words with DA handling of officer-involved shooting
"I saw the yellow tape right there at the end of the street, and I was like, what the hell happened on my block. Then come to find out it happened in my hotel," said CW Hotel resident Roy Talley.
While police say much still remains under investigation, they confirmed that the suspect was known to them.
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SFPD says it plans to release more information in the coming days.
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"Within 10 days, the San Francisco Police Department will be conducting a town hall meeting for its commitment to accountability and transparency, and we will provide information as it becomes available," Rueca said.
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They say this is the second time this year San Francisco police have fired on someone.