The 38-capped internationalist was handed a seven-week suspension for a "tip" tackle on Ospreys wing Tom Grabham, and makes his first competitive appearance since February.
His return is a major boost to the club as they look to bounce back from last weekend's home loss to Connacht (32-24), against a Treviso team who have won their last four games in all competitions at home since their narrow Heineken Cup defeat to Leicester (14-13) in December.
Interim head coach Stevie Scott, said: "It's a massive boost to have Nick [De Luca] back in the team ahead of a very tough match.
"He's an experienced, quality international player, and has been buzzing all week to get back out on the pitch.
"He brings a lot of value to the squad and will hopefully help us continue to take further steps in the right direction."
De Luca's re-introduction is one of four changes to the back division as Scott hands starting berths to a trio of the club's top young Scottish talent.
Harry Leonard (20), Dougie Fife (22) and Tom Brown (23) come into the starting side for Piers Francis and Lee Jones (who start on the bench), and the injured Greig Tonks (hamstring).
Vice captain and lock Sean Cox is set to make his 50th appearance for the club in an unchanged pack, while Jones and Francis' selection on the bench is the only change to the substitutes.
Scott added: "We were all very disappointed with our performance against Connacht at Murrayfield last weekend, so first we want to see a reaction to that and a desire to get back on track, especially in the first 20 minutes, in what is always a crucial part of any match.
"Treviso is a notoriously a difficult place to play. They pride themselves on a strong set piece, and have a number of stand out players, including top Italian internationalists, that make them very dangerous team."
Edinburgh Rugby team to play Treviso at the Stadio Monigo on Friday 19 April (kick-off 7.30pm BST), RaboDirect PRO12 Round 21.
15 Tom Brown
14 Dougie Fife
13 Nick De Luca
12 Matt Scott
11 Tim Visser
10 Harry Leonard
9 Greig Laidlaw CAPTAIN
1 Allan Jacobsen
2 Ross Ford
3 Geoff Cross
4 Grant Gilchrist
5 Sean Cox
6 Stuart McInally
7 Hamish Watson
8 Netani Talei
Substitutes
16 Steve Lawrie
17 Robin Hislop
18 John Yapp
19 Perry Parker
20 Robert McAlpine
21 Sean Kennedy
22 Piers Francis
23 Lee Jones
Players unavailable: Alex Allan (ankle), Ben Cairns (knee), David Denton (knee), Jamie Farndale (leg), Roddy Grant (wrist), James King (groin), Chris Leck (shoulder), Willem Nel (family bereavement) Lewis Niven (bicep), Greig Tonks (hamstring), Steven Turnbull (knee), Sep Visser (international duty), Alun Walker (hamstring), Izak van der Westhuizen (ankle).
Guinness PRO12
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