Hanrahan has not played since sustaining an ankle injury in the pre-season defeat at Ulster on August 26, but he has been back in training during the past two weeks and will now hope to get some game time.
Nic Groom is also among the replacements after returning from his honeymoon.
The starting 15 includes Michael Paterson, Jamie Gibson and Ben Nutley, who makes his first start of the season as Saints look to ensure their back row remains strong.
They are missing five key first-team players in that department, with Tom Wood and Teimana Harrison in the England squad to face Argentina, Louis Picamoles playing for France against New Zealand, Calum Clark banned and Sam Dickinson injured.
Paterson moves from four to six, with James Craig taking his place in the second row.
Tom Kessell, who, like Nutley, was so impressive after coming off the bench in last Friday’s win at Worcester, replaces the injured Lee Dickson at scrum-half.
There is also a first Premiership start of the season for Tom Collins as he is on the wing in place of James Wilson, who is benched.
Meanwhile, Newcastle have named former Saints players Joel Hodgson and Don Waldouck in their starting 15 as they look to stop Jim Mallinder’s men making it five successive wins in all competitions.
Saints: Foden; Elliott, Burrell, Hutchinson, Collins; Myler, Kessell; A Waller, Haywood, Brookes; Craig, Day (c); Paterson, Gibson, Nutley.
Replacements: Clare, E Waller, Hill, J Onojaife, Ludlum, Groom, Hanrahan, Wilson.
Newcastle Falcons: Tait; Goneva, Waldouck, Socino, Watson; Hodgson, Young; Vickers, Lawson, D Wilson; Green, Witty; Chick, M Wilson (c), Hogg.
Replacements: Sowrey, Rogers, S Wilson, Civetta, Fonua, Egerton, Connon, Burdon.