Successful treatment with the combination of low dose thalidomide and interferon-α is described in an 89-year-old man who had chronic hepatitis C-related metastatic hepatocellular carcinoma. Thalidomide 100 mg/day and interferon-α2b 3 million units/week were prescribed. After 9 months of the combination therapy, his serum α-fetoprotein level had declined from 24 549 ng/mL to less than 2.76 ng/mL. The recurrent liver tumors decreased in size and the metastatic lung lesions had complete remission after treatment. Combination therapy with lower dose interferon-α and thalidomide, two antiangiogenic drugs with different mechanisms of action, was associated with a good response and was well tolerated in this preliminary study.