Many interventional techniques aimed at achieving nonsurgical ablation of hepatocellular carcinoma have been developed and clinically tested over the last decade. Percutaneous image-guided therapies such as ethanol injection and radiofrequency thermal ablation provide an effective means for treating hepatocellular carcinoma lesions smaller than 3 cm, but do not ensure successful ablation of larger tumors. In view of the limitations of available interventional therapies, there is currently a focus on a multimodality strategy for the treatment of large hepatocellular carcinomas. Combination of transcatheter arterial chemoembolization and ethanol injection overcomes the weakness of each of the two procedures, enhancing local therapeutic effect and long-term survival. More recently, a new technique for single-session ablation of large hepatocellular carcinoma lesions has been devised by combining transcatheter hepatic arterial balloon occlusion/embolization and radiofrequency treatment. This combined approach substantially increases the thermal necrosis volume that can be created with respect to the conventional radiofrequency technique, as a result of the reduction of heat loss caused by convection. In a pilot multicentric clinical trial performed in 62 patients, successful ablation of hepatocellular carcinoma lesions ranging 3.5-8.5 cm in diameter was achieved in 82% of cases in the absence of major complications. This new technique seems to have the potential to replace other interventional methods for the treatment of large hepatocellular carcinoma.