The crash happened near the Handlery Hotel on O'Farrell St. at Cyril Magnin just before 12:30 p.m.
Authorities say it was solo-vehicle crash involving a Ford pickup truck.
Video shot by ABC7 Eyewitness News showed the front damage of the Ford truck which also hit the front end of a delivery truck.
SFPD Public Information Officer Robert Rueca says two pedestrians were taken to the hospital with non-life threatening injuries.
The driver of the truck remained at the scene.
The cause of the crash is under investigation.
The San Francisco Department of Emergency issued an alert via ALERTSF around 1 p.m. asking drivers and pedestrians to avoid the area.
Anyone with information regarding the crash is asked to contact the SFPD at 415-575-4444.