Hepatocellular carcinoma (HCC) is an aggressive malignancy. Early lesions respond well to hepatic resection or liver transplantation. However, only a few of HCC patients are suitable for surgical intervention. External beam radiation and chemotherapy is poorly efficacious. In the last 20 years, HCCs belonging to the radiosensitive tumor group has been confirmed. Along with the development of new radiotherapy technology and facilities, the research about brachytherapy(especially 125I seed implantation therapy) has provoked more interests in the world. Radioactive seed implantation therapy is a form of interstitial brachytherapy, with the property of local “conformal radiotherapy” and the advantages of minimal invasion, convenience, high performance, and minimal adverse effects. It is a promising therapy for HCC, however the dosimetry hasn′t yet been identified and lacks verification in prospective research. This report aims to further explore the best prescription dose and radioactivity for 125I interstitial implantation brachytherapy for HCC.