Rheumatoid arthritis (RA) is an autoimmune rheumatological disease thought to have substantial genetic contributions. Several genetic factors involved in the susceptibility to psoriasis and psoriatic arthritis (PsA) have been identified with genome-wide association studies, including human leukocyte antigen (HLA)-C, junction adhesion molecule 2 (JAM2) and REL. Psoriasis and PsA may share many features in common with RA. We hypothesized that this polymorphism may contribute to RA susceptibility in a Chinese population. We studied HLA-C rs10484554 C/T, HLA-C rs12212594 T/C, HLA-C rs12191877 C/T, JAM2 rs2829866 A/T and REL rs702873 G/A polymorphisms in 520 patients with RA and 520 controls in a Chinese population. HLA-C rs12191877 C/T polymorphism was in complete linkage disequilibrium (LD) (D' = 1.0, r (2) = 1.0) with HLA-C rs10484554 C/T polymorphism. When the HLA-C rs10484554 CC homozygote genotype was used as the reference group, the TT/CT genotypes were associated with a significantly decreased risk for RA (adjusted OR = 0.72, 95% CI = 0.52-0.99, p = 0.044). We found that the HLA-C rs12191877 C/T polymorphism was also associated with a decreased risk of RA. HLA-C rs12212594 T/C, JAM2 rs2829866 A/T and REL rs702873 G/A polymorphisms were not associated with the risk of RA. These results provide evidence that HLA-C polymorphisms are associated with a decreased risk of RA.