Aims: High-risk variants of human papilloma virus (HPV) may cause oropharyngeal squamous cell carcinomas (SCCs). Recent studies have also reported HPV infection in the sinonasal region. However, the relationship between HPV infection and oropharyngeal/sinonasal SCC in Chinese patients has seldom been reported. In this study, we determined the prevalence of HPV infection in 156 Chinese patients with primary oropharyngeal/sinonasal SCC and investigated the relationship between HPV infection and prognosis. Methods and results: HPV infection was conducted by in situ hybridization. Among 156 patients with oropharynx/sinonasal SCC, thirteen cases (eight from the oropharynx and five from the sinonasal tract) were positive for HPV, 7 and 2 of which were positive for HPV type 16/18 and type 31/33, respectively. The expression of p16 and p53 was examined by immunohistochemistry; p16 expression significantly positively correlated with HPV status (69% vs. 13% for HPV positive vs. negative samples, P < 0.001). Univariate survival analysis showed that HPV infection was significantly associated with better survival. However, this association was no longer observed when the data were corrected for age, tumor stage, nodal stage, and p16 expression. Conclusions: The prevalence of HPV infection is relatively low among these Chinese patients with oropharyngeal/sinonasal SCC. HPV infection was not associated with patients' survival, whereas age, tumor stage, nodal stage and p16 expression showed significant association in this study.