Persistent infection by hepatitis C virus is a major risk factor for the development of hepatocellular carcinoma, but the mechanism of hepatocarcinogenesis is unknown. To study the association of hepatitis C virus with hepatocellular carcinoma, we sequenced part of the 5′ untranslated region of hepatitis C virus from the tumor tissue and the surrounding nontumorous liver of three patients with hepatocellular carcinoma. No sequence differences between tumor-derived and liver-derived hepatitis C virus isolates were detected. The conservation of the 5′ untranslated region of hepatitis C virus–not only in infected hepatocytes, but also in neoplastic cells–suggests that the regulatory elements at the 5′ terminus of the viral genome play an important role in the pathobiology of hepatitis C virus. (Hepatology 1994;19:551–553).