Furbank was forced off with concussion after just seven minutes in the Gallagher Premiership season opener at Sale Sharks last Friday.
And, as on that night, Harry Mallinder will step in to replace the England man, making his first Saints start since the win at Worcester Warriors in March.
Tom Wood covers for Harrison at No.8, with Lewis Ludlam back from England duty and back in the back row at seven.
David Ribbans was also released by the Red Rose earlier this week and the lock lines up alongside Api Ratuniyarawa in the second row.
Reece Marshall replaces James Fish at hooker, while Alex Mitchell comes in for Henry Taylor at scrum-half.
Mitchell and half-back partner James Grayson, who start together for the sixth time for Saints, will both be making their 50th appearances for the black, green and gold.
There is some good news among the replacements as Scotland centre Rory Hutchinson has recovered from an ankle injury and is on the bench.
Saints once again got the Covid-19 all clear this week, but they do still have several injuries to contend with.
Furbank and Harrison are joined on the injury list by Mike Haywood (knee), Danny Hobbs-Awoyemi (Achilles), Courtney Lawes (ankle), Ollie Sleightholme (ankle), Kayde Sylvester (achilles) and JJ Tonks (shoulder).
Saints: Mallinder; Tuala, Proctor, Francis, Collins; Grayson, Mitchell; Waller (cc), Marshall, Hill; Ratuniyarawa, Ribbans; Isiekwe, Ludlam (cc), Wood.
Replacements: Fish, Auterac, Franks, Coles, Adendorff, Taylor, Dingwall, Hutchinson.
Harlequins: Brown; Earle, Northmore, Esterhuizen, Murley; Smith, Care; Garcia Botta, Baldwin, Louw; Young, Lewies (c); Lawday, Evans, Dombrandt.
Replacements: Gray, Els, Kerrod, Tizard, J Chisholm, Steele, Lang, Marchant.