Personality refers to a complex organization of tendencies and characteristics that are associated with important life outcomes such as health and disease and can be effective in mediating high-risk behaviors. The aim of this study was to determine the mediating role of spirituality in relation to personality traits with suicidal tendencies and drug abuse. Descriptive correlational research method was used for research purposes. The sample was selected by convenience sampling method. It consisted of 472 second and third grade high school male students in Karaj, Iran. Students’ main personality traits, spirituality, suicidal tendency and addiction tendency were assessed. The results of correlation analysis showed that there is a positive and significant relationship between the neurotic personality traits and mediating role of spirituality and tendency toward suicidal thoughts and drug abuse, while there is a negative and significant relationship between personality traits of extroversion, openness, agreeableness and conscientiousness and the mediating role of spirituality and tendency towards suicidal thoughts and drug abuse. And this relationship can be moderated by spirituality as mediator.