The aim of our meta-analysis was to quantitatively summarize the association of TYK2 gene polymorphisms with autoimmune and inflammatory diseases. 11 studies that included data from 21497 cases and 22647 controls were identified. OR was used as a measure of the effect of the association in a fixed/random effect model. Meta-analysis was performed for six TYK2 gene polymorphisms (rs34536443, rs2304256, rs280523, rs280519, rs12720270 and rs12720356). Significant association was found in rs34536443 (C versus G: OR = 0.76, 95% CI = 0.69-0.84, P < 0.00001; GC + CC versus GG: OR = 0.78, 95% CI = 0.68-0.90, P = 0.0005; CC versus GG + GC: OR = 0.76, 95% CI = 0.28-2.05, P = 0.58; CC versus GG: OR = 0.74, 95% CI = 0.27-2.02, P = 0.56; GC versus GG: OR = 0.78, 95% CI = 0.68-0.90, P = 0.0006) and rs2304256 (A versus C: OR = 0.78, 95% CI = 0.70-0.87, P < 0.0001; CA + AA versus CC: OR = 0.69, 95% CI = 0.59-0.81, P < 0.0001; AA versus CC + CA: OR = 0.75, 95% CI = 0.66-1.00, P = 0.05; AA versus CC: OR = 0.64, 95% CI = 0.47-0.86, P = 0.003; CA versus CC: OR = 0.70, 95% CI = 0.60-0.83, P < 0.0001) in TYK2 gene, but not for the other polymorphisms (rs280523, rs280519, rs12720270, and rs12720356). This meta-analysis demonstrates that autoimmune and inflammatory diseases is associated with TYK2 gene rs34536443 and rs2304256 polymorphisms, but not rs280523, rs280519, rs12720270 and rs12720356.