Background: Oral cavity and oropharyngeal cancer are growing public health concerns worldwide. It is a debilitating disease that could severely cause traumatic impacts on a patient’s emotional, functional, and financial aspects, simultaneously reducing their quality of life. Aim of the study: Assess prevalence of smoking and students' knowledge about oral cavity, and oropharyngeal cancer at Assiut University. Methodology: A descriptive research design was used in this study. Sample: Multistage random samples were used in this study the current study included 925 students at Assiut University. Two tools were used in the study: tool I self-administered questionnaire concerning the personal characteristics of the student, and tool II part one prevalence of smoking, part two knowledge about the effect of smoking on the oral cavity, and oropharyngeal cancer. Results: The study revealed that the prevalence of smoking among the students was 19.2% and 4.9% of students had a good knowledge score about oral cavity, and oropharyngeal cancer, while 74.9% of students had a poor knowledge score, Conclusion: The students show poor knowledge about the effect of smoking on the oral cavity, and oropharyngeal cancer. Recommendation: An educational program should be developed for university students about smoking, oral cavity, and oropharyngeal cancer.