The riminophenazine compound clofazimine has been shown to be a potent inhibitor of hepatocellular carcinoma (HCC) in vitro. Therapeutic benefit was claimed for patients with HCC treated with clofazimine in a recent clinical trial. The current trial was initiated to evaluate response and survival of patients with HCC receiving clofazimine plus doxorubicin. Twenty-eight patients were entered into the study, of whom 27 were evaluable for response and survival. No patients had a complete or partial response, and 9 had stable disease. The median survival time was 7 weeks. Toxicity was mild with yellow pigmentation of the skin resulting from the clofazimine, and leukopenia, nausea, vomiting and mucositis as expected from doxorubicin. Further studies using other riminophenazine compounds are warranted.