Prior studies have revealed that positive parent–child relationships are negatively associated with college students’ depressive symptom. However, the underlying mechanisms of this relation whether specific mediators or moderators are at play are little known. Therefore, the current study examined the potential mediating role of psychological needs satisfaction and the moderating role of mindfulness in the link between parent–child relationships and depressive symptom among college students. A total of 900 college students from Shenzhen, China (53.40% male; M = 19.82, SD = 1.01, range from 17 to 27 years) completed questionnaires regarding parent–child relationships, psychological needs satisfaction, mindfulness, and depressive symptom. This study found that (1) parent–child relationships are negatively related to college students’ depressive symptom; (2) psychological needs satisfaction could be a potential mediator in the link between parent–child relationships and depressive symptom; and (3) mindfulness could moderate both the relation between parent–child relationships and depressive symptom as well as that between psychological needs satisfaction and depressive symptom, and those relations were weaker among college students with high levels of mindfulness than those with low levels of mindfulness. The current study highlights the mediating and moderating mechanisms that may underlie the correlation between parent–child relationships and depressive symptom, which may contribute to the development of more effective intervention and prevention programs for alleviating college students’ depressive symptom.