Background: Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease characterized by destruction of the interlobular bile ducts and a striking female predominance.The aim of this study was to identify associations between estrogen receptor (ESR) gene polymorphisms with the risk of developing PBC and abnormal serum liver tests in a Chinese population.Methods: Thirty-six patients with PBC (case group) and 35 healthy individuals (control group) from the First Hospital of Jilin University were studied.Whole genomic DNA was extracted from all the participants.Three single-nucleotide polymorphisms (rs2234693, rs2228480,and rs3798577) from ESR1 and two (rs1256030 and rs1048315) from ESR2 were analyzed by a pyrosequencing method.Demographic data and liver biochemical data were collected.Results: Subjects with the T allele at ESR2 rs1256030 had 1.5 times higher risk of developing PBC than those with the C allele (odds ratio [OR] =2.1277, 95％ confidence interval [CI] =1.1872-4.5517).Haplotypes TGC of ESR1 rs2234693, rs2228480, and rs3798577were risk factors for having PBC.The C allele at ESR1 rs2234693 was associated with abnormal alkaline phosphatase (OR =5.2469,95％ CI=1.3704-20.0895) and gamma-glutamyl transferase (OR =3.4286, 95％ CI =1.0083-13.6578) levels in PBC patients.Conclusions: ESR2 rs1256030 T allele may be a significant risk factor for the development of PBC.Screening for patients with gene polymorphisms may help to make early diagnoses in patients with PBC.