Retinoic acid-inducible gene-I (RIG-I) is a member of the DExH/D family proteins, and plays an important role in antiviral response via interferon-stimulated genes (ISGs) and type 1 IFN. In this study, the roles of RIG-I in the epithelial cells in the cross-talk between type 2 IFN and inducible chemokines production are high-lighted. The results showed that RIG-I was constitutively expressed in normal surface epithelia lining the colonic mucosa. RIG-I was constitutively expressed in the epithelial cell lines HT-29, and IFN-gamma and TNF-alpha enhanced the RIG-I expression in a dose-dependent manner. IFN-gamma was shown to stimulate CXCL9-11 production, and RNA interference against RIG-I resulted in significant decrease of IFN-gamma-induced CXCL9-11 productions. These results suggest that RIG-I play an important role in the cross-talk between inflammatory cytokines and immune cell trafficking. In conclusion, RIG-I might regulate the gut barrier function in homeostatic and inflammatory conditions.