Objective: The aim of this study was to design and test a model of familial (family communication pattern including conversation orientation and conformity orientation, family conflicts and parental religiosity) and individual (self-esteem, self-efficacy and resilience) factors of substance use tendency in students of University of Mohaghegh Ardabili. Method: The present study was descriptive-correlational of structural equation modeling type. The statistical population of this study included all students of University of Mohaghegh Ardabili in the academic year 2018-2019. From this population, 347 people were selected by cluster sampling. To collect data, the family communication pattern questionnaire, the family conflict subscale; the questionnaire of parental religiosity, the self-esteem scale, the psychological capital questionnaire, and the addiction acceptance scale were used. The data were analyzed by Pearson correlation and structural equation modeling methods. Results: Conversation orientation, conformity orientation, family conflicts, self-esteem, and self-efficacy had significant direct effects on substance use tendency, but parental religiosity and resilience did not have any significant direct effects on substance use tendency. Self-esteem mediated the relationships of conversation orientation, conformity orientation, family conflicts, and parental religiosity to substance use tendency. Self-efficacy mediated the relationship between parental religiosity and substance use tendency, but resilience did not mediate these relationships. Conclusion: In general, the model presented in the research had an acceptable and appropriate fit and can be used as a suitable model in designing and formulating preventive programs for substance use tendency.