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Introduction: Depression is one of the most common psychiatric disorders in the general population, which disappointment is the main cause of it, and can lead to addiction. Therefore, by identifying all affecting factors and, all conditions needed to prevent addiction can be provided. Aim: The purpose of the present study was to determine the prevalence of depression and disappointment and their relationship with Substance addiction tendency among high school students in Divandareh city in 2018. Method: This is a cross-sectional study. All high school students in Divandareh city included in this study. The sample size was 370 people according to the Morgan table. The sampling method was stratified and the tools were the Beck standard Depression and disappointment Questionnaires and the substance abuse questionnaire. Exclusion criteria included disinclination to participate in the study or incorrect completion of the questionnaires. Data were analyzed by T-test, Spearman correlation and Chi-square tests. Results: 370 students were included in this study. The prevalence of disappointment in the study was 66%, On the other hand 265 of students had low depression, 79 had moderate depression and 26 students had high levels of depression. There was a significant relationship among disappointment and GPA (P=0.012), economic status (P=0.006) and smoking history in students (P<0.001). Also depression had a significant relationship with age (P=0.009) and gender (P=0.032) as well. Conclusion: Depression and disappointment play an important role in quality of life and predict addiction tending in adolescents. And that students studied need more mental health services overall.