Background and aims: Cognitive emotion regulation strategies enhance students’ ability to handle emotional and stressful situations and lead to resilient behavior and suitable behavioral performance. The present study aimed to investigate the association of addiction tendency with distress tolerance, self-differentiation, and emotion regulation difficulties mediated by resilience in university students. Methods: This was a descriptive-correlational study using structural equation modeling (SEM). Cluster sampling was used to enroll 314 individuals among all students at the Islamic Azad University of Tehran in the academic year 2020-2021. The research instruments included the Shorter PROMIS Questionnaire (SPQ), the Distress Tolerance Scale-Short Form (DTS-SF), the Self-Other Differentiation Scale (SODS), the Emotion Regulation Questionnaire (ERQ), and Connor-Davidson Resilience Scale (CD-RISC). Data were analyzed by the SEM method using SPSS-26 and SmartPLS. Results: The results showed that distress tolerance (β=0.25, P<0.001) and emotion regulation difficulties (β=0.35, P<0.001) had a significant direct association with resilience. In addition, distress tolerance (β=0.14, P<0.001), self-differentiation (β=0.25, P<0.001), emotion regulation difficulties (β=0.27, P<0.001), and resilience (β=0.22, P<0.001) had a significant direct relationship with addictive tendencies. Moreover, resilience mediated the association of distress tolerance and emotion regulation difficulties with addictive tendencies in college students. Conclusion: The proposed model had the desired fitting based on the results. It is a great step toward understanding factors associated with addiction tendencies in university students. Furthermore, it is an appropriate model, according to which various programs can be developed and designed to prevent addiction tendencies among university students.