Dysfunctions in bottom-up emotion processing (EP), as well as top-down emotion regulation (ER) are prominent features in pathophysiology of major depressive disorder (MDD). Nonetheless, it is not clear whether EP- and ER-related areas are regionally and/or connectively disturbed, and how they are interactively linked to abnormal affective symptoms of MDD. In this study, regional amplitude of low frequency fluctuations (ALFF) and whole-brain functional connectivity (FC) of meta-analytic-driven EP- and ER-related seeds were compared between 20 MDD patients and 32 healthy subjects. Then, we investigated whether the regulatory behavior can be predicted by the ALFF of EP-related seeds, and also whether this prediction is mediated by the ALFF of ER-related seeds. Finally, correlation between depression severity, ALFF and FC of EP- and ER-related seeds was assessed. We found that: (i) MDD is associated with regional/connectivity alterations of EP- and ER-related areas; (ii) the predictive relationship between elevated EP and weaker regulatory behavior is mediated by diminished ER in MDD; (iii) depression severity is correlated with FC of EP- and ER- related areas. Our findings shed new light on neural correlates of EP and ER in MDD.