Human papillomavirus (HPV) is frequently detected in squamous cell carcinoma of tonsil (TSCC) among the Western population. However, the only reported study on Chinese patients in the English literature demonstrated absence of HPV in TSCC. To evaluate the prevalence and clinical significance of HPV-related TSCC in Taiwan, we performed PCR with MY09/MY11 consensus primers and in situ hybridization to study 111 TSCC samples. The results showed that only 12.6% TSCC were HPV-positive. The favorable 5-year survival rate correlated significantly with HPV positivity (p=0.007), female (p=0.046), and early tumor (T) stage (p<0.001), but Cox's regression analysis revealed that only the status of HPV (p=0.04) and T stage (p=0.004) were independent prognostic factors for survival. In conclusion, the prevalence of HPV-related TSCC is much lower in Taiwan comparing with the Western population, and the prognosis of HPV-positive TSCC is better than that of HPV-negative TSCC.