All four of Saints new signings - Theo Fages, Lama Tasi, Dominique Peyroux and Jack Owens - are included in Keiron Cunningham’s 19-man squad.
They will line up alongside winger Adam Swift and prop Alex Walmsley who missed the club’s pre-season friendlies but have recovered from injury.
Stand-off Travis Burns is a notable absentee.
Huddersfield will give Super League debuts to their two overseas recruits, hooker Ryan Hinchcliffe and prop forward Sam Rapira, but Craig Huby, Kyle Wood and Luke Robinson miss the opener through injury.
Last season: St Helens 35 Huddersfield 34, Huddersfield 8 St Helens 11.
Referee: R Hicks.