Humberside Police were called to the River Freshney near Ripon Street at 2.15pm yesterday (Monday) following a car that a body had been seen in the water.
The ambulance service was also called and police officers, with the assistance of a member of the public, got the man out of the river so first aid could be administered.
He was taken by ambulance to the Diana, Princess of Wales Hospital but was pronounced dead a short time later.
The man, who is believed to be from the local area, has not yet been formally identified and a post-mortem examination is due to take place to establish cause of death today.
Enquiries are ongoing to try to determine how the man came to be in the river and to establish the events leading up to his discovery and Humberside Police would like to hear from anyone who may have seen him, a white man aged in his 50s, before he was found at 2.15pm.
The man who assisted officers in removing the victim from the river also left the area without providing his details and officers are keen to trace him.
Any witnesses, and the man who helped at the scene, are asked to ring 101 referring to log 317 of August 24.