Chronic hepatitis C and B are well-recognized and potentially preventable risk factors for hepatocellular carcinoma (HCC) development. Clinical and epidemiological studies suggest that therapy with interferon-⍺ may reduce the overall risk of HCC development in patients with chronic hepatitis C, who achieve sustained virological response, but even in those who fail to eradicate the infection. In chronic hepatitis B, interferon therapy reduces the risk of HCC development in HBeAg-positive and cirrhotic patients who achieve persistent suppression of viral replication, while in HBeAg-negative patients the beneficial effect of interferon-⍺ is not definitively confirmed. The preventive role of interferon-⍺ after potentially curative treatment for HCC in both chronic hepatitis B and C is uncertain due to methodological flaws of the existing studies and prospective randomized controlled trials with pegylated interferon-⍺ are needed to clarify this issue.