Given the broad immunoinhibitory function of PD-L1 and current promising anti-PD-L1/PD-1 therapies in cancer, our work provides valuable insights into IFN-induced PD-L1 elevation in hepatic microenvironment immunotolerance and raises further potential interest in enhancing the anti-HBV efficacy of therapeutic HBV vaccines and IFN-α by blocking PD-L1/PD-1. The gene discussed is IFNA1; the disease is cancer.