BACKGROUND The hippocampus has been reported to exhibit structural and functional alterations in patients with major depressive disorder (MDD). But functional relationships between this area and other regions remain unclear. METHODS Region of interest-based correlation analyses were performed in the resting-state functional magnetic resonance imaging data to examine differences in functional connectivity (FC) of the hippocampus between medication-naïve patients with MDD and healthy adults. Correlation analyses were done between clinical variables and the strength of FC in regions showing group differences. RESULTS Positive FC with the hippocampal-ROIs was seen in bilateral limbic system, subcortical areas, temporal lobe, medial and inferior prefrontal cortex while negative FC was observed in bilateral prefrontal cortex, parietal and occipital cortex and the cerebellum. Group comparison showed impaired functional connections of the hippocampus in MDD, with a lack of negative FC in left hippocampal-ROI to bilateral middle frontal gyrus, as well as decreased negative FC in right hippocampal-ROI to right inferior parietal cortex and the cerebellum. Negative correlations were seen between illness duration and the strength of FC in the prefrontal and parietal cortex. LIMITATIONS An optimized method taking individual variability of hippocampal volume into account is merited for the definition of seed regions and computation of FC. Further studies recruiting subjects with subthreshold depressive symptoms are needed. CONCLUSIONS Abnormal functional relationships between the hippocampus and cortical areas may underlie the pathophysiology of MDD.