Manhunt launched after deadly attack in Melbourne's CBD

Police have launched a manhunt after a deadly assault in the heart of Melbourne.

Police said on Saturday a Seddon man had died in hospital after he was struck in the head by another man on Wednesday.

They said the 44-year-old had been walking on Elizabeth Street from Flinders Street when he was approached by a man and hit on the head.

He sustained significant head injuries and was taken to hospital in a life-threatening condition before he died.

Homicide Squad detectives are appealing for public assistance to locate Todd Menegaldo following the assault.

Detectives have conducted a significant search for Menegaldo in the past few days, police said.

Menegaldo, who also goes by the nickname "Rooster", is described as being approximately 180 to 185cm tall with a thin build.

Police said he has a black and white crossbreed Staffordshire terrier and is known to frequent the Melbourne CBD, in particular the areas around Elizabeth Street and Flinders Street railway station, as well as the Mildura and Bendigo areas.

Menegaldo was last seen wearing a zip-up purple jumper, dark jeans and a yellow beanie.

Police have released images and CCTV of him in the hope someone can provide information regarding his current whereabouts.

Anyone who sights Menegaldo is urged not to approach him and to contact triple zero immediately.

Anyone with information is urged to contact Crime Stoppers or submit a confidential report online.