CyberKnife is a stereotactic radiosurgery system which could be used to treat many tumors and lesions. It provides the surgeon unparalleled flexibility in targeting using a compact light linear accelerator mounted on a robotic arm. Advanced image guidance technology tracks patient and target position during treatment, ensuring accuracy without the use of an invasive head frame. CyberKnife with Dynamic Tracking Software is cleared to provide radiosurgery for lesions anywhere in the body when radiation treatment is indicated. It has often been used to radiosurgically treat otherwise untreatable tumors and malformations. Moreover, this instrument treats tumors at body sites, most of which are unreachable by other stereotactic systems. Compared with conventional radiotherapy, it is fundamentally different that using non-invasive, frameless, no excessive radiation exposure to normal tissue. In oral malignant neoplasm, surgical excision and radiation therapy should be tried first, additionally chemotherapy could be considered. However, after failure of conventional therapies, patients had poor systemic condition and surgical limitation. So, CyberKnife could be a suitable therapy. A 49 years man was referred in recurred mandibular cancer treated by radiotherapy. The tumor was considered inoperable, because of extensive invasion and was not expected to good response to conventional therapies. We experienced a case of CyberKnife after 4 cycle chemotherapies, so we report it with review of literature.