Sykes will become only the fourth second-row to reach a century of appearances for the club, following Grant Gilchrist, Ben Toolis and Fraser McKenzie.
He will bring up the landmark off the bench, having recovered from the bicep injury he sustained against Zebre Parma.
Van der Merwe, who has missed the start of the season with an ankle injury, returns in place of Malelili Satala as one of four changes to the starting XV.
Geordie Gwynn earns a start on the wing after scoring his first Edinburgh try against Toulon last weekend. He replaces Darcy Graham, who is kept out as a precaution after picking up calf tightness on his return to action in the same game.
Double centurion Grant Gilchrist comes into the second-row in place of Callum Hunter-Hill, having made his comeback from a bicep injury off the bench against Toulon.
Liam McConnell is recalled at blindside flanker, with Tom Currie switching to openside in place of Freddy Douglas, who misses out having sustained a concussion in training.
Head Coach Sean Everitt: “We have always had tough games against the Lions, they a good team with a strong set piece and are a threat in transitions. We need an accurate performance to get the result.
“It’s a big moment for Marshall to hit 100 appearances for the club. He has shown huge amounts of commitment to the jersey during his time in Edinburgh, and it’s an achievement that everyone at the club is proud of him for.”
Piers O’Conor continues at full-back, while co-captain Matt Currie and Mosese Tuipulotu link-up once more in midfield.
Hector Patterson, fresh from signing a new contract with the club, starts at scrum-half alongside stand-off James Grayson.
The front row is unchanged, with Pierre Schoeman and Ollie Blyth-Lafferty named at props alongside Ewan Ashman at hooker.
Gilchrist makes his first start of the season, partnering the ever-present Glen Young in the second row.
Co-captain Magnus Bradbury continues at number 8, packing down alongside the young flanker pairing of McConnell and Tom Currie, both 22.
Get a full injury and squad update here ahead of Friday night’s match against the 10bet Lions.
Edinburgh Rugby team to face 10bet Lions at Hive Stadium in the BKT United Rugby Championship
Friday 23 October, kick-off 7.45pm – live on Premier Sports
15. Piers O’Conor (25)
14. Geordie Gwynn (4)
13. Matt Currie (76) CO-CAPTAIN
12. Mosese Tuipulotu (31)
11. Duhan van der Merwe (114)
10. James Grayson (4)
9. Hector Patterson (8)
1. Pierre Schoeman (154)
2. Ewan Ashman (56)
3. Ollie Blyth-Lafferty (18)
4. Glen Young (74)
5. Grant Gilchrist (234)
6. Liam McConnell (26)
7. Tom Currie (12)
8. Magnus Bradbury (155) CO-CAPTAIN
Replacements
16. Harri Morris (20)
17. Jamie Stewart (2)
18. Paul Hill (39)
19. Marshall Sykes (99)
20. Tom Dodd (22)
21. Conor McAlpine (8)
22. Cammy Scott (34)
23. Harry Paterson (29)