Purpose: The purpose of this study was to identify the relationship of self differentiation, self esteem and mental health in adolescents. Methods: Data were collected from 829 adolescents and analyzed using descriptive statistics, t-test, ANOVA, Scheffe`s test, Pearson correlation coefficients and multiple regression with the SPSS 14.0 program. Results: Mental health differed according to grade, level of father`s and mother`s education. Self differentiation and self esteem had a significant negative correlation with mental health. Stepwise multiple regression analysis showed emotional cutoff, family projection, cognitive emotional function, and family regression in self differentiation, self esteem, level of mother`s education explained 24.4% of the total variance in mental health. Conclusion: The findings indicate that self differentiation and self esteem have an influence on mental health. We need to develop and provide nursing intervention programs to prevent and manage adolescent`s mental health problems and include the family in these programs.