Emotions, cognitions, and defenses are considered as fundamental psychological processes. These complex and multidimensional variables have intertwined relationships with each other. Discovering the novel aspects of these variables and their relationships has theoretical and clinical importance. The purpose of the present study was to examine the mediating role of cognitive emotion regulation strategies on the relationship between alexithymia, anger and anger rumination with ego defense styles. A total of 378 students (227 females, 148 males) from University of Tehran participated in this study. Participants were asked to complete the Farsi version of the Toronto Alexithymia Scale (FTAS-20), Multidimensional Anger Inventory (MAI), Cognitive Emotion Regulation Questionnaire (CERQ), and Defense Style Questionnaire. Alexithymia, anger, and anger rumination revealed significant negative correlations with mature defense style as well as significant positive correlations with immature defense style. Adaptive emotion regulation strategies showed significant positive correlations with mature defense style, while maladaptive emotion regulation strategies showed significant positive correlations with neurotic and immature defense styles. Based on the results of path analysis, cognitive emotion regulation strategies did not play a significant mediating role on the relationship between alexithymia and defense styles. The results of this study indicated that mediating effect of maladaptive emotion regulation strategies on the relationship between anger and anger rumination with immature defense style was stronger than the other variables. Also mediating role of cognitive emotion regulation strategies in case of anger rumination and defense styles was more stronger than anger and defense styles. Based on the results of the present study, it is concluded that the relationship between alexithymia, anger, and anger rumination with defense styles is not a simple linear one, but the other variables such as cognitive emotion regulation strategies play a mediating role in this relationship. Results of the present study were a novel step to conceptualize a theoretical model in predicting ego defense styles.