Patients affected by hepatocellular carcinoma (HCC) with unfavorable prognostic factors have limited therapeutic options due to moderate responsiveness to chemotherapeutic agents and lack of compliance with such treatments. In this study the feasibility and efficacy were evaluated of a treatment with mitoxantrone(dihydroxyanthracenedione, DHAD), 12 mg/m2 i.v. on day 1 every 3 weeks. We included 18 patients with poor-risk HCC ineligible for our other trials in relation to their performance status [8], pretreatments [6], age over 70 years [5], severe concomitant illness [6], and altered blood count [platelets less than 100,000/mm3) [8]. Of 17 evaluable cases, there were 4 partial remissions (23%) (95% confidence interval, 10-47%), 6 no changes, and 7 progressions. There were no drug-related deaths, and side effects were moderate and documented only in a few cases. Median survival of evaluable patients was 5 months (range, 1-15). The results were comparable with those obtained with adriamycin but without important toxicity. We conclude that DHAD seems to be safe and moderately active in poor-risk HCC.