Background: Self-medication is a common and regular practice of using medicines without any medical supervision by the people themselves for self-treatment. Aim of this study: to assess knowledge and reported practices of university students regarding self-medication and determine the prevalence of self-medication among university students at Assuit University. Subjects and Methods: a descriptive cross sectional study was used in this study which conducted at four faculties of Assiut University among 1035 of fourth grad who were selected through simple random sample. Two tools were utilized for data collection: Tool I: A structured self-administered questionnaire Tool II: to assess reported practices of self-medication among university students. Results: It was found that 76.2% of studied students were females and the prevalence rate of self-medication among them was 90.4% also 71.4% of them reported that fast solution to relieve pain was the most common reason for using self –medication. 84.4% and 62.1% of studied students had unsatisfactory knowledge and reported practices regarding self –medication. Conclusions: The prevalence of self-medication was high among university students in Assuit University. Most of studied students had un satisfactory knowledge and reported practices about self- medication. Recommendation: Periodic health education programs regarding self-medication are needed to enhance awareness among studied students.