Hepatectomy was once regarded as the only curative therapy for hepatocellular carcinoma (HCC). Non-surgical percutaneous tumor ablation techniques such as a percutaneous radiofrequency ablation (RFA), have been introduced and now play an important role in the treatment of HCC. The survival rate of HCC patients after ablation therapy is similar to that of patients who underwent surgical resection. Moreover, we have recently reported that after tumor ablation, interferon therapy may enhance patient survival, almost equal that of patients who underwent liver transplantation. The age of patients with HCC has been increasing worldwide; therefore, they are much more likely to demand a minimally invasive procedure for HCC. Hence, combined therapy of percutaneous tumor ablation and interferon will become an increasingly important option for treatment of HCC patients.