This paper assessed the antitumor activity and toxicity of neoadjuvant paclitaxel, cisplatin, and 5-fluorouracil (TCF) in locally advanced squamous cell carcinoma of head and neck cancer (HNC). Between October 2009 and December 2010, 42 patients were enrolled. Median age was 52.3 years (range, 36 - 70 years). Male/female 13/1. 61.9 percent had associated with alcohol and tobacco. 8 patients were stage III, 34 stage IV. Squamous cell carcinoma grade II was 76.2 percent. The completed rate was 35.7 percent, the partial rate was 47.6 percent. Acute toxicities grade 3 were mainly neutropenia 5 pts, leukopenia 6 pts, erythrocytes 2 pts. The other toxicities were lower. In conclusion, the neoadjuvant chemotherapy TCF in 42 patients with locally advanced head and neck squamous cell carcinoma was tolerable, with encouraging efficacy and acceptable toxicities. However, the authors needed to continue follow-up patients for a long time.