Background Self-medication among student nurses is the use of medicines without doctor’s prescription. This practice is a global phenomenon and potential contributor to human resistance to most drugs characteristic with many health challenges. Despite the high knowledge on the complication of self-medication, studies showed that most student nurses still practice self-medication. Aims To assess the reasons for increase in self-medication and control measures among student nurses in school of nursing, University of Benin Teaching Hospital, Edo State, Nigeria. Materials and Methods A descriptive cross-sectional survey was conducted with stratified simple random sampling technique to select 90 student nurses from three different levels in school of nursing, University of Benin Teaching Hospitals in Benin-City, Edo State. A self-structured questionnaire with open and Likert scale questions used as instrument was administered to assess the reasons for increase in self-medication and the control measures. Data collected were analyzed using tables, percentages, means, standard deviation and t-test for inferential statistics at 0.05 level of significance, through Statistical Package for Social Sciences software. Results The result showed the reasons for increase in self-medication and how to reduce its occurrence. It also showed that, the gender of the student nurses is statistically related to the reasons why they practice self-medication (t=6.82, P=? 0.001). Conclusion Self-medication can be reduced among student nurses by empowering the law enforcement agencies against self-medication, improving the availability of essential and quality drugs in school clinics, and inclusion of all student nurses in health insurance scheme program, where they can enjoy the benefit of paying only 10% of the treatment charges.