Backgrounds: A p16 protein is known to be overexpressed in human papillomaviruspositive head and neck squamous cell carcinoma specimens. p53 is a tumor suppressor protein detectable by immunohistochemistry in carcinogen-associated head and neck squamous cell carcinoma as a result of gene mutations. Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor of the Erb-B family. The purpose of this study is to investigate the prognostic impact of p16 and p53 and EGFR expression in oropharyngeal squamous cell carcinomas. Methods: This was an observational and cross sectional study. We retrospectively examined the relationship between prognosis, and p16 and p53 and EGFR expression levels of oropharyngeal squamous cell carcinoma specimens in 100 patients using immunohistochemistry. Results: An increase in the TNM stage and pathological tumor size status correlated with an increase in EGFR expression. In the cases with lymphovascular invasion, the expression was detected at a higher ratio. Cases in which high levels of pl6 and p53 expression were observed did not show any lymphovascular invasions. Conclusion: Expressions of p16, p53 and EGFR were considered to be most effective in early carcinogenesis stages of oropharyngeal SCC. In comparison with p16, p53 and EGFR expression levels were observed to be associated with poor prognostic parameters and were higher at later stages of oropharyngeal SCC carcinogenesis development.