Apoptosis signals are essential for establishing homeostasis and adequate immune response. Dysregulation of apoptosis-related genes in the immune system, which could be due to gene polymorphisms, conduct to autoimmune diseases including rheumatoid arthritis. In the current study, the apoptosis-related gene Fas_-670A>G, FasL_844C>T, and FasLIVS2nt_124A>G polymorphisms were genotyped in 120 Iranian patients with rheumatoid arthritis (RA) and 112 unrelated healthy controls using PCR-RFLP method. Among the 120 RA patients being heterozygous in the promoter region of Fas_-670A/G (OR 1.42,CI 0.92-1.52, P = 0.18) and FasL_-844C/T (OR 1.42, CI 0.92-1.52, P = 0.18) and homozygous in the minor allele for FasLIVS2nt_124G/G (OR 1.43, CI 0.76-1.81, P = 0.7), the frequency of these polymorphisms is higher in the cases than in controls and the elevated risk of RA were observed when the patient compared with controls, although this is not statistically significant.