Evidence indicated that inflammatory response and some pattern-recognition receptors play important roles in the occurrence and progression of osteoarthritis. This study is conducted to evaluate the role of RIG-I and its adaptor protein MAVS in the pathogenesis of osteoarthritis. Four SNPs in gene and four in gene were genotyped in 1056 Chinese Han population. We also overexpressed MAVS in murine chondrogenic ATDC5 cells and analyzed the cell viability and apoptosis. Rs11795343 (P: 0.063394) in , rs17857295 (P: 0.073518) and rs7262903 (P: 0.054052, P: 0.067930) in were marginally associated with OA. Rs7269320 (P: 0.014783, P: 0.03272) in was significant associated with OA. Further analyses in different genders indicated that rs7262903 (P: 0.017256, P: 0.045683) and rs7269320 (P: 0.013073, P: 0.038881) are significantly associated with OA in female group. Haplotype analyses indicated G-C-G (χ: 4.328, P: 0.037503) in rs10813821-rs11795343-rs659527 block of , G-C-A-T (χ: 4.056, P: 0.044028) and G-C-C-C (χ: 14.295, P: 0.000158) in rs17857295-rs2326369-rs7262903-rs7269320 block of were significantly associated with OA. Furthermore, forced expression of MAVS could suppress the viability and promote the apoptosis of ATDC5 chondrogenic cells. In conclusion, this study indicated that RIG-I and MAVS are probably associated with OA in the females of Chinese Han population. And MAVS might be a novel risk factor for OA which may involve in growth of chondrocytes and cartilage homeostasis.