Abstract：Objective: To investigate the associations of single nucleotide polymorphism of (SNP) of rs77418916 and rs8108402 in miR-181 with the risk of systemic lupus erythematosus (SLE) in the Chinese population of Guangxi. Methods: The lymphocyte subsets were analyzed by flow cytometry. The SNPs of miR-181 gene were detected by single nucleotide primer extension assay with SNaPshot and DNA sequencing method. The relative expressions of miR-181a and miR-181c in mononuclear cells were detected by real time RT-quantitative PCR. Results: The polymorphism of rs8108402 locus contained CC, CT and TT genotypes. The frequencies of CT and TT genotypes as well as the dominant and recessive model were different significantly between SLE group and control group (CT vs CC: OR=1.50, 95%CI: 1.03 to 2.19, P=0.033; TT vs CC: OR=2.65, 95%CI: 1.18 to 5.98, P=0.019; CC/CT vs TT: OR=2.23, 95%CI：1.01 to 4.93, P=0.048; TT/CT vs CC: OR=1.61, 95%CI：1.12 to 2.31, P=0.010). The polymorphism of rs77418916 locus contain AA, AT and TT genotypes, but no association between rs77418916 polymorphism and susceptibility of SLE was found. The relative expressions of miR-181a and miR-181c genes in SLE group were down-regulated compared with control group (Z=-3.22, P＜0.01 and Z=-3.24, P＜0.01, respectively), and the patients carrying rs8108402 CT and TT genotype showed lower level of miR-181c compared with the patients carrying CC genotype (Z=-2.51, P＜0.05). The absolute numbers of CD3⁺, CD4⁺, CD8⁺ and NK cells were decreased significantly in SLE group compared with that of control group (P＜0.01). Conclusion: The polymorphism of miR-181c rs8108402 may associate with the susceptibility of Chinese SLE patients in Guangxi region. The risk of SLE may increase in the individuals caring CT or TT genotype by decreasing the expression of miR-181c gene.