"The club can announce this evening that it has parted company with Head Coach Mike Phelan," Hull said in a statement.
"The search for a replacement has begun and an announcement will be made in due course."
Phelan is the third Premier League manager to lose his job in less than two weeks, after Alan Pardew was sacked by Crystal Palace and Bob Bradley by Swansea City at the end of last year.
Phelan, 54, had been appointed caretaker in succession to Steve Bruce in July before being handed a permanent contract in October after Hull made a bright start to the season.
Yet a series of injuries to key players took their toll and Hull, who were promoted last season, soon dropped down the table and Phelan has paid the price for a lengthy winless run that has left them bottom with just 13 points.
Gary Rowett, the former Birmingham City manager, was an early favourite with British bookmakers to replace him.