We administered trientine hydrochloride, a drug used in the treatment of Wilson's disease, to patients with hepatocellular carcinoma after radical treatment with percutaneous ethanol injection or radiofrequency ablation, and examined its effect on the reduction of liver-tissue copper content. We enrolled 24 patients with 3 or fewer primary lesions of Child class A or B hepatocellular carcinoma with diameters of 3 cm or less who had undergone radical treatment with percutaneous ethanol injection or radiofrequency ablation. Trientine hydrochloride was orally administered in a single daily dose of 250 mg to 12 patients before a meal (at fasting, group 1) or at a total daily dosage of 750 mg, divided into 3 doses, to 12 patients (group 2). This study was a randomized between-groups comparative study of 12 weeks' duration. We used the particle-induced x-ray-emission method to determine liver-tissue mineral content. Urine copper and serum mineral levels were also measured, and transaminase levels were examined. Liver-tissue copper content decreased significantly, to 160.1 microg/g dry weight, after treatment, compared with the pretreatment level of 306.8 microg/g dry weight (P <.05). We detected no significant difference in iron or zinc content before and after treatment. The copper content was significantly reduced after treatment in both groups (P <.05). The urine copper level was significantly increased after 1 week of treatment but decreased thereafter. Serum copper levels were significantly reduced after treatment (P <.01). We detected no significant difference in transaminase level before and after treatment. Iron-deficiency anemia in 1 patient after 12 weeks' treatment was the only adverse reaction, and it was improved by the administration of an iron product. We noted no other overt adverse reactions. In patients with hepatocellular carcinoma, trientine hydrochloride therapy may significantly reduce copper content in liver tissue.