Stress is a universal concept and all human beings have likely experience stress in their lifetime. The aim of this correlational study was to examine self-esteem in the relationship between irrational beliefs and perceived stress in adolescents. The data of the research were collected from adolescents studying in a high school located in the Southeastern Anatolia Region. The study group of the research consisted of a total 310 high school students, 177 female (57.1%) and 133 male (42.9%). The mean age of participants in the study was 16.43 (SD=1.20). In order to gather data "Irrational Beliefs Scale for Adolescents", "Rosenberg Self Esteem Scale" and "Perceived Stress Scale" were used as measures. In the analysis of the data, Pearson correlation analysis, descriptive statistics, Ordinary Least-Squares Regression and Bootstrap Method were used. According to the results of the research, the mediating role of self-esteem in the relationship between irrational beliefs and perceived stress was found statistically significant. The research findings were discussed within the context of the related literature and some suggestions were provided for researchers and practitioners in the field of mental health.