Objective To explore the characteristics of spontaneous neural activities at resting in firstepisode of childhood and adolescent depressive disorder with non-suicidal self-injury (NSSI). Methods A total of 50 first-episode children and adolescents with depressive disorder, who met the diagnostic criteria of depressive disorder in the fifth edition of American Diagnostic and Statistical Manual of mental disorders (DSM-5) in the mental health center of the First Hospital of Hebei Medical University from February to June 2021 were selected as patient group. According to DSM-5, the patients were evaluated for NSSI behavior and divided into two groups: NSSI group (n=27) and non-NSSI group (n=23). At the same time, 50 healthy volunteers were recruited as the control group. All enrolled patients were evaluated with the 24-item Hamilton Depression Scale (HAMD24) for depressive symptoms. Low frequency amplitude (ALFF) analysis was used to investigate the characteristics of local spontaneous neural activities at resting in first-episode of childhood and adolescent depressive disorder with NSSI. Results There were statistically significant differences of ALFF values in the left orbitofrontal gyrus, right precuneus, left superior temporal gyrus, left thalamus, right caudate nucleus and right hippocampus in the NSSI group, non-NSSI group and control group (F=-4.54, -4.79, -4.48, 5.35, 4.49, 5.39; P< 0.05, GRF correction). Compared with those in non-NSSI group, the left thalamus and right caudate nucleus showed higher ALFF values, and the right precuneus showed lower ALFF values in NSSI group (t=4.84, 4.76, -6.02; P < 0.05, GRF correction). Conclusions The local spontaneous neural activity of emotional regulation and self-perception related brain regions (such as left thalamus, right caudate nucleus and precuneus)were abnormal at resting-state in first-episode of childhood and adolescent depressive disorder with NSSI.