This association study was designed as a retrospective study, including 657 patients with chronic HBV infection (CHB) and 299 healthy controls. All subjects were ethnic Han Chinese. CHB patients recruited between 2012 and 2015 at The First Hospital of Jilin University (Changchun) were further classified into non-HCC (n = 370) and HBV-related HCC (n = 287) patients. Frequency matching by age and sex was performed for each group. CHB patients were defined by persistent or intermittent elevations in alanine transaminase level (≥ 2 times the upper limit of normal) and elevated HBV DNA levels for at least 6 mo. HBV-related HCC was diagnosed based on (1) positive results on computed tomography (CT), magnetic resonance imaging or ultrasonography; and (2) combined positive findings upon cytological or pathological examination. The non-HCC patients included CHB and LC patients, characterized by active necro-inflammatory liver disease without/with fibrosis on imaging examination without evidence of HCC, according to the guidelines for the prevention and treatment of CHB (2010 version), and the diagnostic criteria (10th National Conference on Viral Hepatitis and Hepatopathy 2000, China). All samples were HBV-positive, but hepatitis C virus (HCV)-, HIV-negative, according to serology tests and infection history. Exclusion criteria included the presence of autoimmune and other liver diseases, alcoholic liver disease, hemorrhagic liver disease, and intra- and extra-hepatic bile duct stones. The criteria for healthy participants included no previous diagnosis of cancer or liver-associated illness. Healthy individuals were recruited from The First Hospital of Jilin University during the same period. All patients were further confirmed as being negative for hepatitis B surface antigen, hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb), hepatitis B virus core antibody, and hepatitis C antibody, as measured by chemiluminescence methods (Roche E411, Basil, Switzerland). We also collected demographic data of each subject, such as smoking and drinking status. Individuals who smoked daily for at least 1 year were defined as smokers, and those who consumed alcoholic drinks more than once per wk for over 6 mo were considered drinkers. Written informed consent was obtained from all patients, and this study was approved by The First Hospital Ethical Committee of Jilin University.