<p>Background: Rheumatoid Arthritis (RA) is a debilitating disorder in which the immune system mainly targets the synovial tissue. Janus kinase family including tyrosine kinase 2 (TYK2) is one of the crucial mediators of the downstream signaling pathway of inflammatory cytokines that further contributes to RA pathogenesis. In this study, the association of <em>TYK2</em> gene rs34536443 polymorphism, which may affect the function of TYK protein and, hence, the inflammatory settings, with RA susceptibility was investigated. Moreover, its correlation with demographic and serological features of the patients was assessed.&nbsp;<br /> Methods: In the present study, 700 RA patients and 700 sex, age and ethnicity-matched healthy individuals as the control group were included. MGB TaqMan real-time allelic discrimination method was used to determine the rs34536443 polymorphism. Rheumatoid factor, anti-cyclic citrullinated peptide antibody, erythrocyte sedimentation rate and C-reactive protein were also measured.<br /> Results: The frequency of rs34536443 minor allele (C allele) was not different between patients and control group [1.7 <em>vs</em>. 2.61 percent, OR (95% CI)=1.35 (0.78-2.33);p=0.27]. There was not a statistically significant association between rs34536443 genotypes and RA susceptibility. Genotypes of rs34536443 polymorphism were associated nor with demographic neither with serological features of RA patients.&nbsp;<br /> Conclusion: In the present study, there was not any association between <em>TYK2</em> gene rs34536443 polymorphism with either disease susceptibility, demographic and serological features of Iranian RA patients. These findings are not compatible with previous works from other ethnicities, further supporting the role of genetics in disease susceptibility.</p>