Making his first Six Nations start, Henderson will form a back row partnership with his Ulster colleague Chris Henry and Ireland vice-captain Jamie Heaslip.
Paul O'Connell leads the side and packs down in an unchanged front five alongside Devin Toner, Cian Healy, Rory Best and Mike Ross.
Jonathan Sexton has recovered from a thumb injury to take his place in the back-line that started against both Wales and England.
There are a two changes on the bench with Rhys Ruddock replacing the starting Henderson and Eoin Reddan coming in for Isaac Boss who is rested this week.
Meanwhile, Brian O'Driscoll will become the most-capped player in Test rugby history this weekend when making his 140th Test appearance (132 matches with Ireland and eight outings for the British & Irish Lions).
IRELAND Team & Replacements (v Italy, 2014 RBS 6 Nations Championship, Aviva Stadium, Saturday, March 8, kick-off 2.30pm):
15. Rob Kearney (UCD/Leinster) 52
14. Andrew Trimble (Ballymena/Ulster) 53
13. Brian O'Driscoll (UCD/Leinster) 131
12. Gordon D'Arcy (Lansdowne/Leinster) 77
11. Dave Kearney (Lansdowne/Leinster) 5
10. Jonathan Sexton (Racing Metro 92) 41
9. Conor Murray (Garryowen/Munster) 25
1. Cian Healy (Clontarf/Leinster) 45
2. Rory Best (Banbridge/Ulster) 73
3. Mike Ross (Clontarf/Leinster) 37
4. Devin Toner (Lansdowne/Leinster) 13
5. Paul O'Connell (Young Munster/Munster) (capt) 90
6. Iain Henderson (Ballynahinch/Ulster) 8
7. Chris Henry (Malone/Ulster) 12
8. Jamie Heaslip (Dublin University/Leinster) 63
16. Sean Cronin (St. Mary's College/Leinster) 33
17. Jack McGrath (St. Mary's College/Leinster) 6
18. Martin Moore (Lansdowne/Leinster) 3
19. Rhys Ruddock (St. Mary's College/Leinster) 1
20. Jordi Murphy (Lansdowne/Leinster) 1
21. Eoin Reddan (Lansdowne/Leinster) 52
22. Paddy Jackson (Dungannon/Ulster) 8
23. Fergus McFadden (Old Belvedere/Leinster) 24