Background: Certain genetic polymorphisms can lead to differences in immunity function, resulting in different clinical outcomes for hepatitis B virus (HBV) patients. The aim of this study was to investigate the association between apolipoprotein E (ApoE) gene polymorphisms and HBV infection status in northern Chinese individuals. Methods: Genomic DNA was extracted using an improved sodium iodide (NaI) method from the peripheral blood of 270 patients with hepatitis B and 112 healthy controls. Multiplex Amplification Refractory Mutation System (Multi-ARMS) was performed to analyze ApoE gene polymorphisms with three alleles (epsilon 2, epsilon 3, epsilon 4) in patients and controls. A chemiluminescence assay was used to detect serological markers for hepatitis B infection status. Results: An improved PCR system for the detection of ApoE gene polymorphisms was established successfully. The frequency of the epsilon 2 allele in patients with HBV infection was higher than that of normal controls (p<0.05). The epsilon 2 allele, compared with the epsilon 3 and epsilon 4 alleles, showed positive correlation with the different HBV infection models wodds ratio (OR)=1.735, 95% confidence interval (CI): 1.509-1.999, p<0.01; OR=1.768, 95% CI: 1.554-2.011, p<0.01]. The OR for the ApoE epsilon 2 allele was 1.503 in a multivariate unconditional logistic regression model (OR=1.503, 95% CI: 1.212-1.754, p<0.01). Conclusions: Our results indicated that the ApoE gene polymorphism was associated with HBV infection, and the epsilon 2 allele showed positive correlation with HBV infection in northern China. Clin Chem Lab Med 2010; 48:1803-7.