Young adolescent has to prepare for a global successful adult life of competition and independent functioning which is possible only through enhancing their psychosocial competencies through life skills training. As a health care provider, the school nurse is in a unique position to act as health educator, a change agent for youth substance abuse prevention. This study aims to evaluate the effect of life skills intervention on social self-efficacy for prevention of drug abuse among young adolescent students at Benha City. Methods. A quasi-experimental design was utilized. The study was conducted at two Preparatory Schools in Benha City (Benha Preparatory School for Boys and Benha Shared Preparatory School). Simple random sample of 120 students were included in the present study. Two tools were used for data collection; first tool. The Children’s Self-Efficacy in Peer Interactions (CSPI). It was used to measure confidence in social interactions. Second tool; The Life Skills Training Questionnaire-Elementary Student (LSTQ-ES). This tool is designed to measure changes in knowledge, attitudes, and behaviors of elementary students related to social confidence and drug resistance skills. Results. The mean age of the studied students was 14.9±0.45 years. There were statistically significant improvements (P