Objective: To explore the chain mediating effect of cognitive flexibility and depressive cognition between mindfulness and suicide risk in undergraduates. Methods: Suicidal Behaviors Questionnaire-revised (SBQ-R), mindful attention awareness scale (MAAS), cognitive flexibility inventory (CFI) and depressive cognition scale (DCS) were used to investigate 2 627 freshmen from a medical university in Guangdong Province. Results: The scores of suicide risk, mindfulness, cognitive flexibility and depressive cognition were (M(Q_R)): 4.00(2.00), 67.00(15.00), 78.00(13.00), 5.00(7.00), respectively.The results of correlation analysis showed that suicide risk was positively correlated with depressive cognition (r=0.280, P<0.01), and negatively correlated with the level of mindfulness and cognitive flexibility (r=-0.253, r=-0.196, P<0.01). Mindfulness was positively correlated with cognitive flexibility (r=0.539, P<0.01), negatively correlated with depressive cognition (r=-0.518, P<0.01). Cognitive flexibility was negatively correlated with depressive cognition (r=-0.584, P<0.01). Mediation modeling analysis showed that mindfulness had a significant direct effect on suicide risk.The direct effect value was -0.101, accounting for 34.9% of the total effect.The total indirect effect of mindfulness on suicide risk was -0.188, accounting for 65.1% of the total effect.The mediating effect of cognitive flexibility as mediator between mindfulness and suicide risk was -0.063, accounting for 21.8% of the total effect.The mediating effect of depressive cognition as mediator between mindfulness and suicide risk was -0.054, accounting for 18.7% of the total effect.The chain mediating effect of cognitive flexibility and depressive cognition was -0.071, accounting for 24.6% of the total effect. Conclusion Mindfulness can influence suicide risk, not only through the direct path, but also through the indirect path of cognitive flexibility and depressive cognition, as well as the chain mediating path between these two variables.