6086 Background: The standard treatment for locally advanced tongue cancer is surgery. However, the patient’s quality of life is lost. As a newly non-operative treatment, we report the efficacy and toxicity of proton beam therapy combined with selective intra-arterial infusion chemotherapy (PBT-IACT) for locally advanced tongue cancer. Methods: Between February 2009 and August 2012, 45 cases of stage III-IV(M0) squamous cell carcinoma of the tongue (28 men and 17 women) were treated by PBT-IACT at Southern TOHOKU Proton Therapy Center. Median age was 58 years (range:24-83 years), and clinical stage III/IVA/IVB were 11/32/2 respectively. In case of surgery, the patients required subtotal or total resection of the tongue. Initially, 2 courses of systemic chemotherapy and prophyractic whole neck irradiation (36Gy/20fr.) were performed. Subsequently, for gross tumor targets, PBT (33Gy/15fr.) and IACT were administered via the superficial temporal artery by continuous infusion of cisplatin with sodium thiosulphate. For PBT, 1 or 2 portals of 210 MeV proton beam were arranged in optimal angles to avoid overdosing the risk organ. Systemic chemotherapy was performed only for age of 70 years or younger. Results: The median follow-up was 27 months (range:8-48 months). Over all survival (OS), disease-free survival (DFS), and local control (LC) rates at 2 years were 88%,78%, 80%, respectively. LC of cervical lymph node metastases at 2 years was 86%. As the early toxic event, grade 3 mucositis (32/45) and blood/bone marrow toxicity (22/45) were observed. Within 6 months after this therapy, mandibular osteomyelitis occurred in 1 case. Conclusions: PBT-IACT appeared to be safe and has a good LC rate for locally advanced tongue cancer. Furthermore, it is not inferior to surgery and can be one of the new effective treatment options for locally advanced tongue cancer.