Objective To identify the associations of single nucleotide polymorphism (SNP) loci rs2910164, rs3746444, rs2292832 and rs11614913 of miR-146a, miR-499a, miR-149 and miR-196a with rheumatoid arthritis (RA) in a Chinese Han population. Methods A case-control genetic association study was carried out in 600 patients with RA and 398 healthy individuals. The four SNPs were selected for genotyping by multiplex polymerase chain reaction and ligase detection reaction. Results The rs3746444 CT genotype was correlated with the activity and severity of RA in Chinese Han population. Moreover, gene-sex (rs11614913-sex) interaction was identi?ed by GMDR analysis. However, we did not ?nd any signi?cant association of rs2910164, rs2292832 or rs11614913 with RA risk, severity, or activity. Conclusions The miR-499a polymorphism (rs3746444) is associated with the disease severity and activity of RA, which needs further replication and validation.