Loneliness has been recognized as a pressing global health threat. Research shows that loneliness is associated with depressive symptoms, but less is known about what factors might influence this relationship. This study tested the hypothesis that mindfulness would buffer the association between loneliness and depressive symptoms. A total of 220 Chinese adults completed validated measures of loneliness, mindfulness, and depressive symptoms. Hierarchical multiple regression and moderator analyses were conducted. Mindfulness was significantly associated with depressive symptoms (β = -.485, p < .001) after controlling for demographic variables and loneliness. Furthermore, mindfulness was a statistically significant moderator. Loneliness was more strongly associated with depressive symptoms when the levels of mindfulness were low. Mindfulness buffered the association between loneliness and depressive symptoms. Encouraging mindfulness practices might offer community-wide benefits from a public health perspective. While some studies showed that mindfulness could reduce loneliness, future studies should further evaluate whether mindfulness-based programs could also prevent the mental health consequences of loneliness.