STORY: Ambulances rushed to the scene on the packed Istiklal Avenue, which police quickly cordoned off. The area, in the city's Beyoglu district, had been crowded as usual at the weekend with shoppers, tourists and families.
State broadcaster TRT and state-owned Anadolu agency said the cause of the blast was not yet known.
"Four people were killed and 38 others were wounded according to initial reports," Istanbul Governor Ali Yerlikaya said on Twitter, adding the explosion occurred around 4.20 p.m. local time (1320 GMT).
The nearby Kasimpasa police station told Reuters all crews were at the scene but gave no further details.
Local media said inspectors were on the scene and Anadolu reported the Istanbul chief public prosecutor's office launched an investigation into the blast. The Turkish Red Crescent said blood was being transferred to nearby hospitals.
Turkey's RTUK regulator imposed a broadcast ban on coverage of the blast around an hour after it occurred.