The aim of the present study was to deliver a high internal radiation dose to small hepatocellular carcinoma (HCC) lesions in an attempt to treat this disease. A total of 18 patients with HCC lesions measuring less than 4.5 cm in diameter (25 lesions) were treated with superselective intra-arterial injection of I-131-labeled Lipiodol (370-1,100 MBq in 3-5 ml) using a 5-F or coaxial catheter. All the lesions were nodular, multinodular, or hypervascular on pretreatment angiography. In all, 15 lesions that received over 180 Gy of cumulative radiation decreased in size in proportion to the Lipiodol retention on CT, and no pericapsular recurrence was found on angiography after 14-54 months of follow-up. In five patients who subsequently underwent surgery, 65% to 100% tumor necrosis was detected. No abnormal change in liver function tests or untoward clinical symptom of the lung, thyroid, or bone marrow was detected in patients who survived for more than 3 years after the treatment. Superselective high-dose internal radiation therapy of small HCC offers hope of treatment and long-term local control without complications.