A 60-year-old male with hepatocellular carcinoma was treated by repeated intra-arterial injection of epirubicin, carboplatin and doxorubicin. Subsequently, radiotherapy and intravenous administration of etoposide were also carried out. Thirty-three months later he developed AML (M2). The chromosome analysis revealed 45, X, -Y, t (8;21) (q22;q22), which suggested that this leukemia was induced by topoisomerase II targeting agents. He was treated with low dose BHAC and G-CSF and achieved complete remission. This leukemia may be caused by synergic effect of topoisomerase II inhibitors and carboplatin together with radiotherapy. This may be the first report of therapy-related leukemia following chemotherapy for hepatocellular carcinoma.