Objective To investigate the effect of inhibiting the mitochondrial inner membrane protein OMA1 on rotenone (Rot)-Induced apoptosis in a Parkinson’s disease (PD) cell model. Methods SH-SY5Y cells were cultured in vitro, treated with Rot (final concentration of 0. 05, 0. 1, 0. 2, 0. 3 or 0. 4 μmol/ L) for 24 h, and the best Rot concentration (0. 2 μmol/ L) was selected for subsequent experiments. The cells were divided into a control group (without special treatment), PD model group (0. 2 μmol/ L Rot treatment for 24 h), negative control group (control group which was transfected with OMA1 negative sequence), and OMA1 siRNA group (0. 2 μmol/ L Rot treatment for 24 h and transfection with OMA1 siRNA). CCK-8 was used to detect cell survival rate, and an inverted phase-contrast microscope was used to observe cell morphology in each group. Western blot was used to detect changes in the expression of OMA1 and the apoptosis-related proteins Caspase-3, Bax and Bcl-2, and a TUNEL apoptosis kit was used to detect cell apoptosis. Results Compared with the control group, the survival rate of SH-SY5Y cells decreased in a concentration-dependent manner with increasing Rot concentration (P<0. 05). Compared with the control group, the PD model group’s expression of OMA1 and the apoptotic protein Caspase-3 and the ratio of Bax/ Bcl-2 were increased (P<0. 01). Compared with in the PD model group, in the OMA1 siRNA group cells, morphological changes gradually restored, apoptotic protein Caspase-3 expression decreased, Bax/ Bcl-2 increased, and TUNEL apoptosis staining suggested reduced apoptosis (P< 0. 01). Conclusions Inhibition of the mitochondrial inner membrane protein OMA1 ameliorated the apoptosis induced in the Rottreated PD cell model, and in turn, may have a protective effect on neurons.