Head and neck squamous cancer is a major concern in India. The proportion of advanced cases is significantly high, and these patients have dismal survival prospects despite aggressive therapy. Often surgical resection and/or radiotherapy are not feasible in these patients. Hence, we decided to explore the option of neoadjuvant chemotherapy using effective agents like ifosfamide and paclitaxel in combination with cisplatin in these patients. A total of 361 patients were evaluable at the end of study. Of these, 207 had received ifosfamide and cisplatin and 154 had received taxanes (paclitaxel or docetaxel) in addition to ifosfamide and cisplatin. The ifosfamide-cisplatin group had an overall response rate of 66.67% (CR, 16.42%; PR, 50.24%) and the median duration of response was 5.5 mo; whereas the group in which taxanes were added, showed an overall response rate of 73.37% (CR, 7.79%; PR, 65.58%) with a median duration of response of 10 mo. The toxicity in both the groups was acceptable and there was no mortality. We conclude that taxane-based combinations have a significant activity in advanced head and neck squamous cancer and warrant further studies.