Aim– To compare the onset and severity of acute toxicities in advanced head and neck cancer patients undergoing hyperfractionation as compared to conventional CT–RT (concurrent chemo–radiation). Method– 100 patients with squamous cell carcinoma of head and neck region were randomly assigned to either hyperfractionation or conventional CT–RT. Hyperfractionation arm received 74.8 Gy 68 fractions, 1.1 Gy per fraction, 2 fractions per day with an interval of 6 hours. While standard arm received 66.6 Gy 37 fractions, 1.8 Gy per fraction with concurrent Cisplatin 40mg/m2 .Onset and severity of acute toxicity were observed weekly. Result– Onset of acute toxicity like dermatitis, mucositis and laryngitis was within 1st week of treatment in hyperfractionation arm which was statistically significant (P=0.001, P=, 0.01, P=0.04 respectively). No significant difference in the onset of pharyngitis or xerostomia was observed between the 2 arms. In terms of severity, statistically significant grade 3 toxicity were observed in the hyperfractionation arm (dermatitis P=0.045, mucositis P=0.001, laryngitis P=0.002, pharyngitis P=0.002 and xerostomia P= 0.02). Grade 4 toxicity was observed in the pharynx, larynx and mucous membrane in the hyperfractionation arm. Conclusion– Hyperfractionation leads to earlier onset and more severe acute toxicity (grade 3 or above) in advanced head and neck cancer which leads to treatment delays and loss of therapeutic gain.