Turkish President Recep Tayyip Erdogan said an explosion on Istiklal Avenue was caused by a “bomb attack”.
Speaking before his departure to the G20 summit in Indonesia on Sunday, Erdogan said the explosion was a “treacherous attack” and its perpetrators would be punished.
Four people died at the scene and two in the hospital, Erdogan said.
Another 53 were wounded, according to information he received from Istanbul Governor Ali Yerlikay, who said the explosion occurred about about 4.20pm on Sunday (12.30am Monday AEDT).
Five prosecutors were assigned to investigate the explosion, state-run Anadolu news agency said.
A video posted online showed flames erupting and a loud bang, as pedestrians turned and ran away.
Other footage showed ambulances, fire trucks and police at the scene. The cause of the explosion was not clear. Social media users said shops were shuttered and the avenue closed down.
Broadcaster CNN Turk said 11 people were injured.
The avenue is a crowded thoroughfare popular with tourists and locals, lined by shops and restaurants.
Turkey was hit by a string of deadly bombings between 2015 and 2017 by the Islamic State group and outlawed Kurdish groups.