Chronic hepatitis B virus (HBV) infection is a major public health problem in China. We evaluated the impact of psychosocial factors (stigma, disclosure, depression, and anxiety) on health-related quality of life (HRQoL) among people living with chronic HBV infection (CHB) in the city of Dalian, Liaoning Province, China. In this hospital-based cross-sectional study, 401 patients living with chronic HBV infection were enrolled as study participants. Study measures included the Beck depression and anxiety inventory, the WHO Quality of Life (WHOQOL-BREF) assessment, the Toronto Chinese HBV Stigma Scale, and disclosure of HBV status to sexual partners. The primary outcome was HRQoL score as measured by the WHOQOL-BREF. A linear regression model was used to examine the association between HRQoL and the potential risk factors including stigma, disclosure, depression, anxiety, and sociodemographic variables. Stigma, disclosure, depression, and anxiety were the covariates of interest. A majority of the participants were females (n = 251, 65.6%), married (81.6%), and had a college or higher degree (32.4%). Depression, anxiety, stigma, and disclosure of HBV infection were associated with low HRQoL in all four domains of the WHOQOL-BREF (physical, psychological, social, and environmental domains) (P < 0.05), when all psychological factors were included in the model separately. Depression was found to be independently associated with low HRQoL in people living with HBV, when all psychological factors were included in the model simultaneously (P < 0.0001). Our data indicate the urgent need for healthcare providers (HCPs) and policy-makers to implement psychological interventions to improve HRQoL among people living with CHB.