Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease. To date, the specific mechanisms that drive RA disease remain unknown and provide the impetus for genetic investigations into the development of RA. Researchers hope to identify gene polymorphisms that could serve as treatment targets in patients with RA. We have previously suggested that the gene encoding the pro-inflammatory adipokine resistin (RETN) may correlate with RA development. In this report, we sought to determine whether selected RETN single nucleotide polymorphisms (SNPs) are associated with RA susceptibility and clinicopathological characteristics. Four RETN SNPs (rs3745367, rs7408174, rs1862513, and rs3219175) were assessed using TaqMan genotyping in Chinese Han patients with RA and healthy controls. We found that carriers with the C allele of the RETN SNP rs7408174 as well as those with the AG allele or who had at least one A allele of the SNP rs3219175 are at greater risk of developing RA disease compared with wild-type carriers. Moreover, RA patients with the AG allele of the RETN SNP rs3219175 had higher serum C-reactive protein expression compared with controls, and these patients had a high likelihood of being on tumor necrosis factor (TNF) inhibitor therapy. This study is the first to discuss risk factors associated with RETN SNPs in RA progression in a Chinese Han population.