INTRODUCTION Whether the recent advances in antiviral therapy including nucleos(t)ide analogue (NA) or interferon (IFN) impacts the management of patients with virus-related hepatocellular carcinoma (HCC) remains unclear. AREA COVERED The beneficial effects of antiviral therapy on HCC patients receiving curative treatment, transhepatic arterial chemoembolization (TACE), or radiotherapy are reviewed and discussed. EXPERT OPINION For patients with HCV-related HCC after curative treatment, interferon (IFN)-based therapy has been shown to improve the survival and reduces the risk of HCC recurrence. However, it carries the risk of adverse effects, especially in cirrhotic patients. Therefore, the benefit of IFN should be weighted against its risk in each individual. For patients with HBV-related HCC after curative treatments, antiviral treatment with NA has been found to improve liver function, overall survival, and possibly reduce the risk of HCC recurrence. In contrast, these benefits were not consistently observed in those receiving IFN treatment. In HCC patients receiving palliative TACE or radiotherapy, HBV reactivation occurs in a small proportion of them, and preemptive NA treatment can reduce the risk of hepatitis flare due to viral reactivation. Therefore, NA treatment after curative treatments or TACE is strongly recommended for HCC patients with high viral load (HBV DNA> 2000 IU/mL).