Interleukin (IL)-35, a recently identified cytokine of the IL-12 family, is a potent immunosuppressive cytokine secreted by regulatory T (Treg) cells and the newly reported regulatory B (Breg) cells. IL-35 functions as a crucial immunosuppressive factor in immune-mediated diseases, and the predominant mechanism of suppression is its ability to suppress T cell proliferation and effector functions. The pathogenic processes of the non-cytopathic hepatitis B virus (HBV) infection-related liver diseases are immune-mediated, including liver damage and viral control. It has been found that IL-35 is detectable in peripheral CD4(+) T cells in chronic HBV-infected patients, whereas it is undetectable in healthy individuals. There is growing evidence that cytokine-mediated immune responses play a pivotal role in determining the clinical outcome during HBV infection. It is particularly important to investigate the effects of IL-35 in the immunopathogenesis of chronic HBV infection. In this study, the recent understanding of this issue is discussed.