The safety and antibody responses of coronavirus disease 2019 (COVID-19) vaccination in patients with chronic hepatitis B (CHB) virus infection is still unclear, and exploration in safety and antibody responses of COVID-19 vaccination in CHB patients is significant in clinical practice. 362 adult CHB patients and 87 healthy controls at an interval of at least 21 days after a full-course vaccination (21-105days) were enrolled. Adverse events (AEs) were collected by questionnaire. The antibody profiles at 1, 2 and 3months were elucidated by determination of anti-spike IgG, anti-receptor-binding domain (RBD) IgG, and RBD-angiotensin-converting enzyme 2 blocking antibody. SARS-CoV-2 specific B cells were also analysed. All AEs were mild and self-limiting, and the incidence was similar between CHB patients and controls. Seropositivity rates of three antibodies were similar between CHB patients and healthy controls at 1, 2 and 3months, but CHB patients had lower titers of three antibodies at 1month. Compared to healthy controls, HBeAg-positive CHB patients had higher titers of three antibodies at 3months (all P<.05) and a slower decline in antibody titers. Frequency of RBD-specific B cells was positively correlated with titers of anti-RBD IgG (OR=1.067, P=.004), while liver cirrhosis, antiviral treatment, levels of HBV DNA, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and total bilirubin (TB) were not correlated with titers of anti-RBD IgG. Inactivated COVID-19 vaccines were well tolerated, and induced effective antibody response against SARS-CoV-2 in CHB patients.