Objective To explore the association between estrogen receptor gene polymorphism and systemic lupus erythematosus in women of Han nationality from Jiangxi province. Methods Whole blood samples were obtained from 95 female patients with SLE of Han nationality （18 with pre-menarche onset and 77 with post-menarche onset） and 100 healthy female controls from Jiangxi province. Genomic DNA was extracted from these samples followed by the analysis of polymorphism at PvuⅡand XbaⅠsites of estrogen receptor alpha gene with PCR-restriction fragment length polymorphism （RFLP）. The frequencies of alleles and genotypes were compared between the control and patients and between patients with pre-menarche onset and those with post-menarche onset. Results The frequency of P allele was higher in patients with SLE than in the controls （35.8% vs 27%, P < 0.05）, but lower in patients with pre-menarche onset than in those with post-menarche onset （19.4% vs 39.6%, P < 0.05）. Further more, an increment was observed in the frequency of Xxpp genotype in patients with pre-menarche onset compared with normal controls and patients with post-menarche onset （16.7% vs 1% and 1.3%, both P < 0.05）. Conclusions The frequency of P allele in ER alpha gene is increased in female patients with SLE of Han nationality from Jiangxi province. The Xxpp genotype of ER gene may be associated with the susceptibility to pre-menarche onset SLE.