ObjectiveThere is no objective method to diagnose major depressive disorder (MDD). This study explored the neuroimaging biomarkers using the support vector machine (SVM) method for the diagnosis of MDD. Methods52 MDD patients and 45 healthy controls (HCs) were involved in resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Imaging data were analyzed with the regional homogeneity (ReHo) and SVM methods. ResultsCompared with HCs, MDD patients showed increased ReHo in the left anterior cingulum cortex (ACC) and decreased ReHo in the left precentral gyrus (PG). No correlations were detected between the ReHo values and the Hamilton Rating Scale for Depression (HRSD) scores. The SVM results showed a diagnostic accuracy of 98.96% (96/97). Increased ReHo in the left ACC, and decreased ReHo in the left PG were illustrated, along with a sensitivity of 98.07%(51/52) and a specificity of100% (45/45). ConclusionOur results suggest that abnormal regional neural activity in the left ACC and PG may play a key role in the pathophysiological process of first-episode MDD. Moreover, the combination of ReHo values in the left ACC and precentral gyrusmay serve as a neuroimaging biomarker for first-episode MDD.