Background: The tendency to the use of drugs is a daily increase, especially among adolescents. We conducted the present study to investigate the role of self-efficacy in predicting drug-seeking behaviors among high school students in Jahrom, Fars province, Iran. Methods: This cross-sectional study was performed on high school students in Jahrom, Fars province, Iran in 2020. The sample size was estimated to be 405 people who were chosen using multi-stage cluster sampling. The data collection tools here included demographic information questionnaire, Iranian Addiction Potential Scale, and self-efficacy questionnaire Children Scale. Data analysis was performed with SPSS version 21 using descriptive statistics and Pearson’, s correlation coefficient, Independent t-test, One-way ANOVA, and Linear regression. Results: There was a significant inverse correlation between self-efficacy and drug-seeking behaviors (r=-598, P<0. 001). Additionally, the results revealed a relationship between grade, father’, s job, mother’, s education, and smoking history in friends and parents with self-efficacy (P=0. 002, P=0. 012, P=0. 004, P=0. 006, P=0. 005, respectively) and drug-seeking behaviors (P<0. 001). Father’, s job, friends’,smoking history, and self-efficacy were significant factors inversely associated with drug-seeking behaviors (P=0. 003, P<0. 001, P<0. 001, respectively). Conclusion: High levels of self-efficacy of students and educated families can play a protective role against drugs use. Further focus on prevention, especially on capacity building and the empowerment of young people can reduce the tendency to use drugs.