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Recent introduction of all-oral direct-acting antiviral (DAA) treatment has revolutionized care of patients with chronic hepatitis C virus infection. Because patients with different liver disease stages have been treated with great success including those awaiting liver transplantation, therapy has been extended to patients with hepatocellular carcinoma as well. From observational studies among compensated cirrhotic hepatitis C patients treated with interferon-containing regimens, it would have been expected that the rate of hepatocellular carcinoma occurrence is markedly decreased after a sustained virological response. However, recently 2 studies have been published reporting markedly increased rates of tumor recurrence and occurrence after viral clearance with DAA agents. Over the last decades, it has been established that chronic antigen stimulation during persistent infection with hepatitis C virus is associated with continuous activation and impaired function of several immune cell populations, such as natural killer cells and virus-specific T cells. This review therefore focuses on recent studies evaluating the restoration of adaptive and innate immune cell populations after DAA therapy in patients with chronic hepatitis C virus infection in the context of the immune responses in hepatocarcinogenesis.