Background: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by inflammation. It mainly affects joints and nearby tissues. Tumor necrosis factor (TNF) is the main role-player in the pathogenesis of RA. It binds to both TNF receptors namely TNF-RI and TNF-RII. Several studies have indicated a relationship between the TNF-RII 196R/R genotype with increased production of cytokines and susceptibility to inflammatory diseases and autoimmune disorders. Objectives: Therefore, the present study aimed to investigate the association between TNF-RII polymorphism and RA. It also aimed to study the predictive value of the TNF-RII 196R allele for patients' susceptibility to RA. Methods: A total of 100 patients and 100 controls were enrolled in the study and their peripheral blood DNA was extracted. Allelic discrimination was performed between case and control groups to investigate the association between the functional TNF-RII 196R polymorphism and RA. Screening analysis for genotyping of TNF-RII functional polymorphism was performed by the TaqMan allelic discrimination assay using real-time PCR. Results: There was a significant difference between cases and controls in terms of the distribution of TNF-RII genotypes (TT, TG, GG). Correlation analysis showed an association between the G mutant allele and functional 196R polymorphism (CI = 95%, OR = 2.6, P = 0.035). Conclusions: According to our results, there is a significant correlation between TNF-RII polymorphism and the risk of RA.