Our purpose was to study necrosis and apoptosis of hepatocellular carcinoma (HCC) cells after preoperative transcatheter arterial chemoembolization (TACE) with use of low-dose and high-dose anticancer drugs in HCCs. Fifty-four patients with advanced but surgically resectable HCC were studied. Thirty-four patients who elected to undergo preoperative superselective TACE were randomized to low- and high-dose TACE. Patients in group A (n = 16) received low-dose anticancer drugs: 2 mg mitomycin C (MMC), 10 mg epirubicin (EPI), and 100 mg carboplatin (CBP). Patients in group B (n = 18) were given high doses of anticancer drugs (10 mg MMC, 40 mg EPI, and 300 mg CBP). Hepatic resection was subsequently performed. Group C comprised 20 patients who underwent resection without TACE. In all patients the necrosis rates and apoptosis index of tumor cells were evaluated by pathologic examinations and terminal deoxynucleotidyl transferase-mediated nick-end labeling assay. There was no significant difference between group A and group B in tumor response (p [ 0.05) after TACE. Necrosis rates in groups A, B, and C were 88.4 +/- 11.1%, 87.1 +/- 12.5%, and 7.3 +/- 3.5%, respectively. There was no significant difference between group A and group B (p [ 0.05), while statistical difference was found between group A and group C (p \ 0.001) and between group B and group C (p \ 0.001). Apoptosis indexes in the three groups were 11.0 +/- 4.0%, 10.7 +/- 3.9%, and 5.6 +/- 2.6%, respectively. Statistical difference exhibited between group A and group C (p \ 0.001) and group B versus group C (p \ 0.001). No significant difference was observed between group A and group B (p [ 0.05). In conclusion, superselective TACE with low- and high-dose chemotherapeutic agents induced similar degrees of cellular apoptosis and necrosis.