Awake craniotomy is a common procedure in resection of lesions near critical functional regions, particularly the speech and motor areas. During awake craniotomy, patients need to be fully alert and cooperative during testing. On the other hand, it is desirable to keep them sedated, avoiding discomfort, anxiety and pain over the rest of the surgery. In this case report, we report our successful use of dexmedetomidine-fentanyl combination for sedation in intracranial tumor resection with awake craniotomy. Dexmedetomidine-fentanyl combination was well tolerated in this adolescent patient and provided good surgical conditions and patient comfort during tumor resection and testing.