Introduction: Pain in advanced head and neck cancer is intractable and many a times difficult to manage with pharmacological agents. Sphenopalatine ganglion (SPG) block provides excellent pain relief in patients who are suffering from various types of orofacial pain. Role of radiofrequency ablation (RFA) of SPG is described for orofacial cancer pain. Aim: The aim of the study was to observe efficacy and duration of pain relief by RFA of SPG in advanced head and neck cancer patients. Materials and Methods: Thirty-three patients suffering from advanced head and neck cancer were enrolled in this study between September 2013 and February 2016. All patients underwent RFA of SPG, under fluoroscopy guidance following a successful diagnostic block of SPG with local anesthetic. Pain was assessed before the procedure, immediately after the procedure, and during each follow-up visit. Follow-up visits were weekly for 4 weeks and then monthly till the end of life. Patients were continued on oral morphine, but the dose was reduced to one-third of total dose and was adjusted according to patients' requirement during each follow-up. Duration of analgesia, morphine requirements, and incidence of complications were noted. Results: There were 32 males and one female. Mean age of patients was 43.24 ± 13.52 (mean ± standard deviation [SD]), ranging from 19 to 58 years. Three patients did not undergo RFA due to cheek hematoma formation during the procedure. Visual analog score was reduced from 8.43 ± 1.10 (preprocedure) to 1.36 ± 1.61 (postprocedure) (mean ± SD). Mean duration of analgesia was 17.55 ± 26.12 (mean ± SD) weeks. Mean reduction in the dose of morphine was from 124.65 ± 46.78 to 40.00 ± 18.05 mg (mean ± SD) immediately after the procedure. One patient was followed up for 30 months. Sixteen patients died within 3 months and had good pain relief. None of the patients had any serious complications. Conclusion: RFA of SPG is a good adjuvant method of pain management in head and neck cancer patients. It gives significant pain relief and reduces morphine requirement. It is safe and it can be carried out as day-care procedure.