Background: To evaluate the response and toxicity of docetaxel, cisplatinum, 5-FU vs paclitaxel, cisplatinum, 5-FU as neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiation (CTRT) with weekly cisplatinum in locally advanced head and neck cancer. Methods: 40 locally advanced head and neck cancer patients who satisfied the eligibility criteria were randomized.21 patients received three cycles of NACT i.e paclitaxel (175 mg/m²) on d1, cisplatinum (30 mg/m²) and 5-FU (600 mg/m²) d2-d4 (TCF) and 19 patients received three cycles of NACT docetaxel (75 mg/m²) on d1, cisplatinum (30 mg/m²) and 5-FU (600 mg/m²) d2-d4 at three week intervals, followed by concurrent weekly cisplatinum 30 mg/m² along with conventional external beam radiation of total tumor dose dose 66 Gy. Response was assessed after NACT and again after six weeks, three months and six months of completion of chemoradiation. Toxicities were assessed after each cycles of NACT and also weekly during CTRT and thereafter. Results: Two weeks after completion of NACT complete response (CR) in TCF was 4.76%, partial response (PR) 80.9% and no response 9.5%. However in DCF, CR was 15.78 % PR was 73.68%. 10.52% patientd died due to toxicity. With a median follow up of seven months, in TCF CR was 57.14%, PR 33.33% and no response was 4.76%, whereas in DCF CR was 78.94%, PR 10.52% and death 10.5%. On evaluation of toxicities during NACT, patients in DCF had more significant neutropenia and in TCF more incidence of neuropathy. During CTRT, in TCF grade II and III mucositis was 54%, grade II neutropenia 5.6%, and grade II anemia 5.3%. In DCF mucositis grade II and III was 49.0%, neutropenia grade II 18.7% and anemia grade II was 7.4%. Late toxicities included were comparable in both arms. Conclusions: With a median follow up of 7 months, the CR in DCF was 78.94%, superior than TCF i.e 57.14%. Neutropenia was significant in DCF and neuropathy was high in TCF. In CTRT mucositis was the commonest toxicity observed in both TCF and DCF which was not statistically significant.