Objective To investigate the association of two single nucleotide polymorphisms (SNPs),rs844648 and rs3850641,in OX40L (TNFSF4) gene,with systemic lupus erythematosus(SLE) in Hubei Han populations.Methods A total of 82 patients with SLE and 100 normal human controls were eligible for this study.Blood samples were obtained from these subjects and DNA was extracted from these samples.PCR-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the genotype of SNPs rs844648 and rs3850641.Results The frequency of AA,AG and GG genotype of the SNP rs844648 was 14.0％,55.0％and 31.0％ respectively in the controls,20.7％,62.2％ and 17.1％ respectively in the patients.A higher frequency was observed for A allele at the SNP rs844648 and G allele at the SNP rs3850641 in patients compared with the normal controls [73.2％ vs.69.0％％,x2 =4.69,P ＜ 0.05,OR =2.182 (1.068 - 4.458);37.8％ vs.24.0％,x2 =4.07,P ＜ 0.05,OR =1.925 (1.015 - 3.651)].The frequency of AA,AG and GG genotype of SNP rs3850641 was 76.0％,21.0％ and 3.0％ respectively in the normal controls,62.2％,31.7％ and 6.1％ respectively in the patients.Conclusions There are polymorphisms in the SNPs rs844648 and rs3850641 in TNFSF4 gene,which may be associated with the development of SLE.