Luke Gale, Jordan Johnstone, Marcus Walker and Aidan Burrell will all depart Hull at the end of the current Super League season.
The quartet will join Manu Ma’u in departing the club, who was announced to be joining Catalans Dragons for the 2023 campaign in July.
Gale, 34, will leave after just one season with the club. The England international made the move to the MKM Stadium on a one-year deal from Leeds during the off-season.
Johnstone, 25, has made 55 appearances since signing ahead of the 2020 season.
Supporters will have the chance to show their appreciation at Saturday’s Hull derby in the final round of the regular season.
Meanwhile, utility-man Will Smith will return to Australia after joining the club on a short-term deal mid-season.
Young pair Marcus Walker and Aidan Burrell both depart having made one appearance each in 2021.
Hull added: “The club would also like to place on record their thanks to Josh Bowden and Josh Reynolds who left the club earlier this season, as well as thanking loan signings Jack Walker, Ellis Longstaff and Josh Simm for their contribution this season.”