North has not played since suffering a knee problem during the Champions Cup defeat to Saracens in October.
He was due to return in one of the recent matches against Ospreys, but suffered a setback.
However, he has come through training unscathed and has been named among the replacements for Big Game 10.
Myler picked up a calf injury in the home defeat to Ospreys earlier this month, but he will also be on the bench at Twickenham.
Saints have made just one change to the side that lost 35-14 at home to Exeter Chiefs last Saturday, with Tom Wood replacing Michael Paterson.
Wood comes in at blindside flanker, with Courtney Lawes reverting to the second row.
Kieran Brookes (hand), Tom Collins (foot), Alex Waller (arm), Jamie Elliott (hamstring) and Rory Hutchinson (back) are sidelined.
Harlequins have made two changes to their team following the narrow defeat to Newcastle Falcons last weekend.
Influential scrum-half Danny Care and No.8 Mat Luamanu come in for Jonno Kitto and Renaldo Bothma respectively.
Harlequins: Brown; Walker, Alofa Alofa, Roberts, Visser; Smith, Care; Marler, Ward (c), Sinckler; Merrick, Glynn; Chisholm, Robshaw, Luamanu.
Replacements: Ella, Boyce, Swainston, Matthews, Wallace, Kitto, Lang, Cheeseman.
Saints: Mallinder; Tuala, Horne, Burrell, Foden; Francis, Groom; Ma'afu, Hartley (c), Ford-Robinson; Ratuniyarawa, Lawes; Wood, Gibson, Harrison.
Replacements: Haywood, van Wyk, Hill, Paterson, Nutley, Reinach, Myler, North.