Background: Globally public health concerns about oral cavity and oropharyngeal cancer are growing. It is a debilitating disease that may result in severe impacts on a patient's emotional, functional, and financial aspects while also significantly 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: In this study, a descriptive research design was used. Sample: The total 925 students from Assiut University participated in the current study, which used multistage random samples. The study utilized two instruments: Tool I was a self administered questionnaire on the student's personal characteristics; Tool II part one was a knowledge test covering the effects of smoking on the oral cavity and oropharyngeal cancer part two the prevalence of smoking. Results: It indicated that 19.2% of students were smokers. 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 knowledge regarding oral cavity and oropharyngeal cancer , and the adverse effects of smoking on the oral cavity is insufficient. Recommendation: An educational program should be given for university students about smoking, oral health, and oropharyngeal cancer.