Many studies have shown that mindfulness can reduce psychological distress; however, the mechanism underlying these effects is still unknown. Along these lines, the mindfulness stress-buffering model provides a hypothesis for explaining the effect of mindfulness on health outcomes through reducing stress. In order to test this model, we investigated the mediating role of stress in the relationship between mindfulness and depression and anxiety. Four hundred and thirty-two university students completed the Mindful Attention Awareness Scale and Depression Anxiety Stress Scale. Data were analyzed by a structural equation modeling using the bootstrap resampling method (k = 10,000) using the AMOS 24.0 software. The results of the mediating model showed that stress fully mediated the relationship between mindfulness and depression and partially mediated the relationship between mindfulness and anxiety in students. Our results suggest that mindfulness, at least partially, yields beneficial effects in reducing depression and anxiety through reducing stress. Therefore, our findings supported the mindfulness stress-buffering model.