Background: Bulky solid tumors contain oxygen-deficient hypoxic areas which cause tumors to become radioresistant. Modification of tumor hypoxia will result in improved outcomes. Objective: To assess and compare the immediate loco regional response rates of locally advanced head and neck squamous cell carcinoma (LAHNSCC) treated with radiotherapy and Nimorazole, with radiotherapy alone to assess the degree of symptom relief and acute toxicities. Methods:30 patients with LAHNSCC with performance status (PS) 3, ineligible to receive concurrent chemotherapy were treated with radiotherapy 50Gy/16# and Nimorazole. The response after 6 weeks was assessed using RECIST criteria. The symptoms present before and after treatment were registered using symptom assessment scale. The toxicities of radiation and nimorazole were documented. Results: 14 among 21 patients with stage IV B showed partial while others had static response. Among the 9 in stage IV A, 6 had complete and 3 had partial response. Overall response rate was 77% compared to 51-73% in historical controls. Significant (>50%) improvement in symptoms was seen in 20 patients (80%). None of the patients developed severe toxicities specific to Nimorazole. 4 patients who developed grade 1 vomiting had dose reduction. None developed rashes or flushing. Conclusion:Hypofractionated radiotherapy along with Nimorazole demonstrated a good response with better symptom control in LAHNSCC patients with poor performance status without added toxicities.