Objective To evaluate the efficacy of ~(125)I radioactive seeds implantation and ~(125)I plaque brachytherapy for oral carcinoma. Methods Eighteen patients with oral carcinoma confirmed by cytology or histopathology were included in this study, Twelve patients with tongue cancer and six patients with gingival carcinoma, there were 20 ulcerative lesions and 10 metastatic cervical lymph nodes. The mean diameter is (2.3±0.7)cm and(2.8±1.7)cm respectively. The patients were treated with both interstitial implantation of ~(125)I seeds and ~(125)I plaque brachytherapy or with ~(125)I plaque brachytherapy only according to patient's individual conditions.The metastatic cervical lymph nodes were treated with CT-guided interstitial implantation of ~(125)I seeds.The sizes of ulcerative lesions and lymph nodes were observed at 1,3,6 months following treatment,and statistical analysis of the sizes of ulcerative lesions were evaluated by paired t-test.Results After 1,3,6 months follow-up,The mean diameters of ulcerative lesions were(2.1±0.6)cm(t=3.559,P＜0.01),(1.7±0.5)cm(t=7.609,P＜0.01),(0.7±0.6)cm(t=11.508,P＜0.01),the cervical lymph nodes showed reduced size. Furthermore, PET-CT images showed a significant decrease in the metabolic activity of treated tumor. After six months, the focus of infection were healing in 8 patients, the cervical lymph nodes of one patient relapsed after ~(125)I implantation again. Patients were followed for 7 to 28 months, all patients were still alive. Conclusion Interstitial ~(125)I radioactive seeds implantation and ~(125)I plaque brachytherapy provide an effective, safe treatment for oral cancer.