The former Bradford Bulls star will come into the side for Mark Foster and make only his second senior appearance since his switch to Kingsholm in October - and will be joined in the side by England full-back Iain Balshaw, who has recovered from a groin injury.
Pryce made his debut in the EDF Energy Cup against Bath in December and his head coach Dean Ryan is thrilled at the prospect of Pryce continuing his development.
"We are still in the early stages of Karl's development but view this as an ideal opportunity to further his progress in the environment of the Premiership," Ryan told www.gloucesterrugby.co.uk
"Karl is starting out on a journey in rugby union and we are excited about him as a prospect. We are not expecting something extraordinary over night because that wouldn't be fair but we will use this as another indicator to his progression.
"Northampton will be a tough place to go but he will have plenty of experience around him and that is very important."
The return of Balshaw is also highly significant considering Olly Morgan is out for the rest of the season with a shoulder problem. Balshaw comes in for Jon Goodridge in the number 15 shirt.
There is also a return for centre Anthony Allen and he will partner Mike Tindall, while up front Italian duo Marco Bortolami and Carlos Nieto also start.
"Balsh has obviously struggled with a sore groin but to have a player of his experience and enthusiasm back is great news," Ryan added. "He will provide an attacking threat and I think our backline looks very competitive.
The half-back combination will see Pete Richards and Ryan Lamb retain their partnership following Gloucester's 33-19 win over Worcester last weekend.
Gloucester's forwards also have a strong look and Nieto will feature in a front row alongside hooker Olivier Azam and loosehead prop Nick Wood.
Luke Narraway retains the number eight shirt in the back row alongside flankers Andy Hazell and Peter Buxton.
On the bench, Willie Walker returns from a shoulder injury and his joined by Haydn Thomas, James Bailey, Mefin Davies, Christian Califano, Will James and Adam Eustace.
"Our performance last week was not acceptable and we will be unable to be that flat tomorrow against a side who have just beaten Leicester," Ryan said.
"We are looking for an improvement but these games are always pretty special, Northampton is a great place to play rugby and we are relishing the opportunity against a side also looking for points."
GLOUCESTER (v Northampton), tomorrow, 3pm: Iain Balshaw; James Simpson-Daniel, Mike Tindall, Anthony Allen, Karl Pryce; Ryan Lamb, Pete Richards; Nick Wood, Olivier Azam, Carlos Nieto, Marco Bortolami (capt), Alex Brown, Peter Buxton, Andy Hazell, Luke Narraway. Reps: Mefin Davies, Christian Califano, Will James, Adam Eustace, Haydn Thomas, Willie Walker, James Bailey.
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