Anxiety is frequently existed in the major depressive disorder (MDD), and more importantly, anxiety often promotes more severe and difficult to treatment for the MDD patients. However, the potential mechanism of how anxiety worsen depression remains unclear.In this study, 75 unmedicated MDD patients and 42 cognitively normal(CN) subjects underwent the resting-state functional magnetic resonance imaging (R-fMRI) scan. Bilateral amygdala were selected to construct amygdala functional connectivity (AFC) networks . Multivariate linear regression analysis was performed to investigate neural substrates of anxiety and depression, as well as the interactive effects of both anxiety and depression on AFC network in MDD patients. Furthermore, mediation analysis was employed to explore whether AFC networks mediate the association between anxiety and depression in MDD patients.Severer anxious symptoms were found in the MDD patients than in the CN subjects. Compared with CN subjects, MDD patients showed a wide-spread reduced functional connectivity in AFC network, including insular, inferior temporal gyrus, temporal pole, fusiform area, hippocampus, parahippocampus and inferior parietal lobe; whilst the increased amygdala connectivity was also found in the posterior cingulate cortex and precuneus within the left AFC network, and in the prefrontal cortex and left superior temporal gyrus within the right AFC network. Multivariate linear regression analysis manifested that the main effects of the anxiety on the bilateral AFC network were illustrated in Figure2A, and main effects of depression on the bilateral AFC networks were observed in the brain regions shown in Figure2B. More importantly, the interactive effects of the anxiety and depression on the bilateral AFC networks were seen in Figure2C. In addition, th­­­­­­e AFC networks correlated with course of disease in MDD patients were marked in Figure2D. Further analysis revealed that MDD patients with lower HAMA scores showed milder depressive symptom and greater AFC strength while MDD patients with higher HAMA scores showed more severe depressive s­­­­­ymptom and lower AFC strength. Beyond that, the mediation effects of AFC networks on the association between anxiety and depression all reached a significant level in MDD patients.The MDD patients showed dysfunctional connectivity in wide-spread AFC network, and these abnormal amygdala connectivity were influenced the trait property in MDD. In addition, common and distinct neural circuits involving anxiety and depression were also separately identified. More importantly, the amygdala connectivity can modulate the effects of anxiety on depression in MDD patients. These findings suggested that the abnormally intrinsic amygdala connectivity could play a crucial role in the neuropathology of MDD combined with anxiety. This research not only demonstrated that there were interactive neural links beneath the comorbidity of anxiety among MDD patients; but also provided some clues for further treatment target on the neural circuits of this comorbidity.