•Disparities in sad face processing exist among different patients with major depressive disorder.•Major depressive disorder is associated with brain function activation of multiple brain areas.•The disruption patterns of brain function differ according to Traditional Chinese Medicine-defined syndromes.•Clinical syndromes of major depressive disorder are associated with abnormalities of functional activation. Objective:Patients with major depressive disorder (MDD) may experience a series of emotional and mental problems accompanied by characteristic clinical symptoms. Depressive patients often have emotional recognition disorders, but the reasons remain unclear. Though a great many functional abnormalities have been observed in the brains of depressed patients, such abnormalities are not often related to clinical symptoms. Currently in Traditional Chinese Medicine (TCM), syndrome differentiation for the MDD mainly consists of excess pattern (EP), and deficiency pattern (DP). EP and DP emphasize balance-regulation thought processes, and are widely used in diagnosis of diseases including depression, anxiety, insomnia, and other emotional disorders. We hope that syndrome differentiation in TCM can combine clinical symptoms and brain function more effectively. The present study investigated altered patterns and different association of brain activation in MDD patients with EP and DP during a facial emotion discrimination task with fMRI. Methods:A total of 45 patients (20 with EP and 25 with DP) and 18 normal controls participated in this study. Whole-brain functional scans were collected for each subject. Different patterns of brain activation and association during the facial emotion discrimination task were analyzed statistically. Results:Comparing all the MDD patients with the normal controls, there were no significant differences for sad vs. neutral condition or for happy vs. neutral condition (corrected p >  0.05). One-way ANCOVA showed significant differences in the left inferior frontal gyrus, the left insula, and the left caudate for sad vs. neutral condition across the DP, EP and NC groups (corrected p <  0.05). The whole brain activation comparison for sad vs. neutral condition between the EP MDD subtype and the DP MDD subtype further verified these differences in the left insula and left inferior frontal gyrus, discovering that these regions showed increased activation in EP MDD subtype compared with the DP MDD subtype (corrected p <  0.05). There were no significant differences in brain activation between each MDD subtype and the normal controls. Conclusion:Disparities in sad face processing exist between MDD patients with different TCM syndrome types, suggesting that TCM syndrome differentiation may provide a biological basis for negativity bias in depression, and may determine both symptom formation and social dysfunction.