CD8(+) T cells are main effector lymphocytes in the control of hepatitis B virus (HBV) infection. However, limitations of model systems such as low infection rates restricted mechanistic studies of HBV-specific CD8(+) T cells. Here, we established a novel immunological cell culture model based on HBV-infected HepG2(hNTCP) cells that endogenously processed and presented viral antigens to HBV-specific CD8(+) T cells. This induced cytolytic and non-cytolytic CD8(+) T-cell effector functions and reduction of viral loads.