Experimental study using nude mice human hepatocellular carcinoma (HCC) xenograft indicated that the combination treatment with iodine 131 (131I)-anti-human HCC isoferritin (131I-isoFtAb), cisplatin, and mixed bacterial vaccine (MBV) yielded better inhibition rate as compared with double combination or 131I-isoFtAb alone. Based on these findings, 25 patients with surgically proven nonresectable and pathologically proven HCC have been treated by radioimmunotherapy using 131I-isoFtAb intrahepatic arterial infusion as a part of multimodality treatment. Of the 25 patients, seven (28.0%) received second-look resection after marked shrinkage of tumor. The 1-year survival was 52.5% (12/23) and 2-year survival 27.7% (five of 18) in the entire series. Of the five patients with 2-year survival, four were in the second-look resection group. Patients with tumor less than or equal to 8 cm showed higher second-look resection rate (62.5% versus 11.8%) and 1-year survival (85.7% versus 37.5%) as compared with tumor greater than 8 cm. Mixed bacterial vaccine as adjuvant immunotherapy seemed effective to prolong survival. The 2-year survival was higher in patients with second-look resection as compared with those without (75.0% versus 14.3%). Thus, radioimmunotherapy using 131I-isoFtAb might be one of the modalities of choice, particularly in the conversion of nonresectable to resectable HCC in a well-designed multimodality treatment regimen.