Background Recent studies have identified signal transducer and activator of transcription 4 (STAT4) as a susceptibility gene for systemic lupus erythematosus (SLE) in different populations In order to examine whether the allele distribution of the single nucleotide polymorphism (SNP) in gene STAT4 rs7574865 in patients with SLE is different from those of healthy controls in Chinese Northern Han population, we investigated whether the variants of STAT4 rs7574865 were associated with any specific clinical features of SLE Methods We genotyped SNPs in STAT4 rs7574865 in 252 patients with SLE and 497 healthy controls All subjects were from the Northern part of Chinese Han population The genotypes in rs7574865 were determined by polymerase chain reaction (PCR) and consequence direct sequencing of PCR products in the DNA samples Results There was a significant difference in distribution of the SNPs in rs7574865 between the SLE patients and healthy controls Compared with healthy controls, there was a significant correlation between TT genotypes in rs7574865 and the risk of SLE when GG genotype was used as a reference genotype after adjusting for gender and age The frequency of T allele in the SLE patients was strongly significantly higher than that of healthy controls Furthermore, there was a significant difference in the distribution of SNP in rs7574865 between male and female SLE patients, when compared with healthy controls The frequency of T allele in rs7574865 in male patients was significantly higher than that of male healthy controls or female patients There was no significant correlation between the frequencies of T allele in STAT4 rs7574865 and the clinical features of SLE Conclusions The SNP rs7574865 in STAT4 is strongly associated with risk of SLE in the Chinese Northern Han population The TT genotype and T allele in STAT4 rs7574869 are susceptibility factors for SLE, especially for male SLE patients Chin Med J 2010,123(22) 3173-3177