BACKGROUND/AIMS: Transhepatic arterial chemoembolization (TACE) is an effective means of treating unresectable hepatocellular carcinoma (HCC). However, it is almost impossible to achieve complete necrosis of tumor by TACE. To achieve complete necrosis of large HCC, we tried a new combination therapy; TACE with percutaneous hot saline injection therapy (PSIT). METHODS: Ninety patients with HCC (2-9cm) were enrolled in this study. Forty-five patients were treated with TACE alone (Group 1), whereas forty-five patients underwent a single TACE session followed by PSIT (Group 2). The therapeutic effect was analyzed by histological evaluation, angiography, ultrasono-graphy and survival rate. RESULTS: The mean numbers of TACE and PSIT were 1.5 and 3.6 times , respectively. On follow- up biopsy for group 2, complete necrosis of tumor was observed in 33 le-sions. Complete remission (CR) and partial response (PR) were achieved more frequently in group 2 than in Group 1. The median survival period was 9 months in Group 1 and 28.9 months in Group 2 (p<0.05). Treatment modality and Okuda stage had a statistical significance in comparing prognosis. The observed side effects of PSIT were transient mild fever and pain during hot saline injection. CONCLUSIONS: The combination therapy of TACE and PSIT appears to be effective in treating patients with unresectable HCC.