We intend to determine the potential benefits and analyze the outcomes of regional intra-arterial infusion chemotherapy (IAIC) for the octogenarian and older patients with oral cancer. Eighteen patients with oral squamous cell carcinoma were included. They were 12 males and six females with ages ranging from 80 to 96 years. An implantable port-catheter system was used for catheterization. Using a portable pump, methotrexate was given continuously through the external carotid artery for a mean period of 5.5 days (range, 4-7 days) followed by weekly bolus of low dose (25mg) of methotrexate until the clinical condition was stabilized. During the first week of IAIC, all tumors began to reduce in size. Of them 11 (61%) had a complete clinical response and 7 (39%) achieved a partial clinical response, after a mean follow-up period of 26 months (range, 8-72 months). The one- and three-year survival rates were 87% and 56%, respectively. There were no catheter-related complications. The side effects were mild and tolerable. IAIC might be specially indicated for oral cancer elderly with co-morbidity since a radical surgery or extensive radiotherapy can be avoided, and offers an acceptable palliative treatment in such patients.