Objective: To explore the relationship between psychological flexibility and Internet dependence among college students, and to verify whether the fear of missing out has a mediating role in it. Methods: A total of 526 college students were tested using the Acceptance and Action Questionnaire, Cognitive Fusion Questionnaire, the fear of missing out questionnaire for college students, Chinese internet addiction scale’s revision. Results: (1) There was a significant positive correlation between experiential avoidance, cognitive fusion, and fear of missing out (r=0.565, p<0.01; r=0.532, p<0.01; r=0.490, p<0.01), and empirical avoidance, cognitive fusion, and fear of missing out (r=0.543, p<0.01; r=0.527, p<0.01); (2) Fear of missing out and experiential avoidance among college students. It has a positive prediction effect on Internet dependence; (3) Fear of missing out played a partial mediating role between psychological flexibility and Internet dependence (β =0.2437, p<0.01). Conclusion: Psychological flexibility and fear of missing out jointly affect college students’ Internet dependence, which provides a new direction for the subsequent research on Internet dependence.