Introduction: Hypopharyngeal squamous cell carcinoma, stage III has poor prognosis with only 25% chance of 5 years of relative survival in such patients in spite of conventional treatment including radical surgery, radiotherapy, and concurrent chemotherapy. Case Presentation: A chronic tobacco-betel nut chewer 62-year-old male patient had dysphagia with hoarseness of voice diagnosed with stage III, grade II malignant pyriform fossa. The patient underwent 9 cycles of neoadjuvant chemotherapy with Inj Paclitaxel 100 mg and Inj Cisplatin 40 mg. He was then referred to our institute for Radical Radiotherapy with concurrent chemotherapy with adjunct Ayurvedic treatment. A total dose of 70 Gy of radiation with cobalt 60 source was administered to the bilateral face and neck, in 35 fractions. Patient also received 6 cycles of concurrent weekly chemotherapy with Inj Cisplatin 40 mg. He received well-planned adjunct Ayurvedic treatment in the form of oral Ayurvedic medicines (OAM) and detoxifying treatment, Panchakarma. All the measured adverse effects of radiotherapy such as Stomatitis, Xerostomia, Taste Alteration, Dysphagia, and Nausea were observed to be remarkably low during and post radiotherapy in this patient. Karnofsky and Quality of Life (QoL) scores revealed patient’s well-being throughout the treatment course. After 5 years, PET CT scan revealed no FDG avid locoregional recurrence or distant organ involvement implying disease-free survival (DFS). Various chemokines, cytokines, and oxidative stress markers were assessed during the course of treatment to observe tumour microenvironment. Conclusion: The present case of Head & Neck Cancer (HNC), stage III, and grade II belonged to high-grade, high-risk hypopharyngeal cancer with poor prognosis. The patient opted for Ayurvedic treatment besides radiotherapy, which continued thereafter for 5 years. We therefore emphasize that in this case, minimum side effects of radiotherapy, immunomodulation, and reduction in inflammation and oxidative stress along with good quality of life can be attributed to OAM and repeated detoxifying Panchakarma treatment supported with healthy diet and good lifestyle. The highlight of the study is the marked effect on the patient’s immune response and reduction in oxidative stress, leading to 5 years and beyond of DFS.

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