ObjectiveWe conducted this resting-state functional magnetic resonance imaging (rsfMRI) study to characterize changes in regional homogeneity (ReHo) or fractional amplitude of low-frequency fluctuations (fALFF) in young adult patients with major depressive disorder (MDD), with or without non-suicidal self-injury (NSSI). MethodsWe recruited 54 MDD patients with NSSI (MDD/NSSI), 68 MDD patients without NSSI, which is referred to as simple MDD (sMDD), and 66 matched healthy controls (HCs). A combination of fALFF and ReHo analyses was conducted. The effects of NSSI on the brain and their relationship to clinical variables were examined in this study. ResultsMDD/NSSI patients have decreased fALFF in the right superior frontal gyrus (SFG) and the right inferior parietal lobe (IPL), decreased ReHo in the right SFG and the right middle temporal gyrus (MTG) and the left middle occipital gyrus (MOG). fALFF and ReHo values of the right SFG are positively correlated. The ReHo values of the right SFG and the number of recent self-injuries are positively correlated; the fALFF values of the right SFG are negatively correlated with NSSI severity. ConclusionsThere is a difference in brain activity between MDD/NSSI and sMDD, which may serve as an important physiological marker to determine the risk of self-injury and suicide. SignificanceAbnormal brain activity in patients with NSSI may provide new perspectives and significant implications on the severity of MDD patients and the prevention of self-injury and suicide.