Coach Pierre Berbizier has made several changes to the side after last weekend's win over Japan, with Castrogiovanni the only member of the front row retained at Ravenhill.
He is partnered in the front row by Fabio Ongaro of Saracens and Salvatore Perugini of Toulouse, with Carlo Festuccia and Andrea Lo Cicero stepping aside. Castrogiovanni wins his 45th cap, while Perugini is just one behind and Ongaro makes his 49th international appearance.
Castrogiovanni's clubmate Geordan Murphy is included on the right wing for Ireland.
Italy: 15 David Bortolussi (Montpellier), 14 Kaine Robertson (Viadana), 13 Gonzalo Canale (Clermont Auvergne), 12 Mirco Bergamasco (Stade Francais), 11 Matteo Pratichetti (Calvisano), 10 Roland De Marigny (Calvisano,), 9 Alessandro Troncon (Clermont Auvergne); 1 Salvatore Perugini (Toulouse), 2 Fabio Ongaro (Saracens), 3 Martin Castrogiovanni (Leicester Tigers), 4 Valerio Bernabo (Brive), 5 Marco Bortolami (Gloucester, captain), 6 Alessandro Zanni (Calvisano), 7 Robert Barbieri (Treviso), 8 Sergio Parisse (Stade Francais).
Replacements: 16 Leonardo Ghiraldini (Calvisano), 17 Matias Aguero (Viadana), 18 Josh Sole (Viadana, 20), 19 Manoa Vosawai (Overmach Cariparma), 20 Paul Griffen (Calvisano), 21 Pablo Canavosio (Castres), 22 Ezio Galon (Overmach Cariparma).