T-cell immunoglobulin and mucin domain-4 (TIMD-4) are likely to impact autoimmune diseases (e.g., rheumatoid arthritis (RA)). It is hypothesized here that TIMD-4 gene polymorphism is likely to display a correlation with the RA risk.For examining the effect exerted by TIMD-4 genetic variant in the RA risk, a case-control study containing 379 RA cases and 432 healthy control groups in Chinese population was performed. This study conducted genotyping with the use of a custom-by-design 48-Plex single nucleotide polymorphism (SNP) Scan™ Kit. Blood serum conditions of TIMD-4 in RA cases and matched control groups were measured by enzyme-connected immunosorbent assay (ELISA).Our results demonstrated that the TIMD-4 rs7700944 polymorphism could increase the RA risk in Chinese population. According to stratification analyzing processes, the TIMD-4 rs7700944 polymorphism displayed the correlation to the elevated RA risk in the females, smokers and cases aged ≥55 years. Cross-over analyses also indicated that the combined effect of smoking or drinking and GA genotype of rs7700944 locus contributed to an elevated risk of RA. In addition, the TIMD-4 rs7700944 polymorphism was also related to RA cases with DAS ≥ 3.20, ESR ≥25.00 mm/h and positive anti-ccp. Moreover, compared with the control groups, the average expression level of TIMD-4 in the serum of RA cases was apparently increased.In conclusion, the TIMD-4 rs7700944 polymorphism may increase the sensitivity to RA in Chinese population.