Background: The results of previous studies indicated that increasing self-compassion is associated with increased ability to regulate emotion. Objective: The aim of this study was to investigate the mediating role of difficulty in emotional regulation in the relationship between self-compassion and anxiety among university students. Materials & Methods: The current cross-sectional study was performed on male and female undergraduate, graduate and doctoral students in Tehran from January to September 2022. After obtaining official permission, 208 students from Amir Kabir University, Shahid Beheshti University, Islamic Azad University, North branch, Central branch, Research Science branch and Rodehen branch were selected using a convenience sampling method. Self-compassion scale of Neff, difficulty in emotion regulation of Graz and Roemer, and Beck anxiety scale were used to collect data. Data were then analyzed using structural equation modeling. Results: The mean age of participants was 27.63 (standard deviation= 9.13), 143 were female and 145 were single. the direct effect of self-compassion on anxiety is not significant (β =0.261, P = 0.109), but the indirect effect of self-compassion on anxiety with mediating role in difficulty of emotional regulation is significant (β = -0.674, P = 0.001). Thus, self-compassion reduces anxiety by reducing the difficulty in emotional regulation. The results also show that self-compassion alone explains 17% of the variance of anxiety. Self-compassion and difficulty in emotional regulation account for 34% of the variance of anxiety. Conclusion: The findings revealed that difficulty in emotional regulation plays a full mediating role in the relationship between self-compassion and anxiety. This study highlights the role of self-compassion and difficulty in emotional regulation in reducing anxiety, But to use self-compassion-based education and emotional regulation in anxiety management, more research is needed to examine their effect in the form of empirical research.