Hepatitis B virus (HBV) infection is common across the world, especially in Asia, Africa, Southern Europe, and Latin America. The association of HBV infection in patients suffering from different oncological conditions is well established. Many cases of HBV reactivation have been reported in patients on immunosuppressive chemotherapy and in patients undergoing hematopoietic bone marrow transplantations. Only one case has been reported so far of HBV reactivation in a patient treated with programmed cell death receptor 1 (PD-1) checkpoint inhibitors in the setting of HIV status. We report a case of a 51-year-old male, former smoker, diagnosed with stage IV poorly differentiated adenocarcinoma of the lung, and started on pembrolizumab, who developed reactivation of chronic hepatitis requiring antiviral therapy.