Objective To investigate the association of single nucleotide polymorphisms (SNPs) of signal transducer and activator of transcription 4 (STAT4) rs7574865 and miRNA146a rs2910164 with rheumatoid arthritis (RA) in Wuling mountain area. Methods 287 RA patients and 305 age-matched healthy controls were included. The rs7574865 and rs2910164 SNPs of RA patients and control subjects were measured by multiplex PCR combined with high throughput sequencing(HI-SNP). The distributions of genotype and allele frequencies in the two groups were analyzed by the Chi-squared test, and also the relationship between these two SNPs and the risk of RA, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (ACCP) antibody were investigated. Results Data showed that the genotype distribution of rs7574865 were significantly different between the cases and controls. The TT genotype and the T allele from rs7574865 were all associated with the risk of RA (OR=2.42, 95%CI: 1.37-4.28; OR=1.43, 95%CI: 1.12-1.82), and dominant and recessive models showed similar results. While, we found miRNA146a rs2910164 has no role in susceptibility to RA, and there was no statistically significant association between the SNPs of rs7574865 and rs2910164 and the level of RF or ACCP antibody. Conclusion STAT4 rs7574865 polymorphism is associated with RA, but not with RF or ACCP antibody levels in Wuling mountain area. In contrast, miRNA146a rs2910164 polymorphism is not correlated with RA.