Introduction: Numerous studies globally confirmed that young prisoners are more susceptible to mental health problemscompared to adult prisoners and the general population. The lack of life skills has been reported as one of the main reasons forthis vulnerability. This study aimed to assess the effectiveness of a life skills education program on mental health and life skillsamong young prisoners in Cambodia. Method: This is an intervention study, applying a ‘difference-in-difference’ analysis. The life skills education program wasimplemented to promote essential skills for mental health and social competence among young prisoners. Mental health and lifeskills competence were evaluated using the Youth Self-Report and Life Skills Development – Adolescent Form scales, respectively.Four prisons were selected from a total of 24 prisons in Cambodia, a post-conflict country in Southeast Asia. A total of 412 youngprisoners aged 15–24 years participated in the study and were randomly assigned to intervention and control groups. Results: Both the intervention and control groups reported decreased mental health problems (DiD=3.78, p=0.34) and improvedlife skills competencies (DiD=0.39, p=0.80) after the intervention; however, the differences were not statistically significant. Conclusion: The life skills intervention program had no significant effect on young prisoners’ mental health and life skillscompetencies. Further studies should be conducted to evaluate the impact of the life skills education program in the prison setting,particularly in low- and middle-income countries (LMICs) such as Cambodia.