Recurrence of hepatocellular carcinoma (HCC) is frequent, even after apparently curative resection. Preoperative transcatheter arterial chemoembolization (TAE) does not improve disease-free survival after hepatic resection. We previously reported the potential usefulness of transarterial immunoembolization (TIE), a newly developed arterial embolization technique using OK-432 and fibrinogen, as preoperative treatment. In this study, we further investigated the effect of TIE by histologic examination of the resected specimens and compared it with conventional TAE in a prospective nonrandomized manner. Thirty-nine patients underwent TIE (n= 17) or TAE (n= 22) before curative hepatectomy for HCC. Transarterial immunoembolization was performed according to the standard protocol using OK-432, fibrinogen, and thrombin. Histologic changes in cancerous and noncancerous liver tissues were examined at different stages after TIE. Histologic grading of cancer cell injury according to the modified Shimosato criteria (Grades 0–IV, in increasing order of severity of cell injury) and postoperative disease-free survival were compared between the two groups. Based on the results of histopathology, TAE was more effective than TIE against the main tumor. In contrast, TIE was significantly more effective than TAE against extracapsular invasion and intrahepatic metastasis. Disease-free survival after hepatectomy tended to be better in patients pretreated with TIE than TAE. Postoperative tumor recurrences in the TIE group (n= 4) occurred in the nontreatment regions, whereas tumor recurrences in TAE group developed mostly (8 of 11 patients) in treated liver regions. Based on results of histologic examination, TIE seems to be more effective than conventional TAE against extracapsular invasion and intrahepatic metastasis. Data for disease-free survival and recurrence site suggest TIE may be a useful preoperative treatment.