Objective To investigate the effect of microRNA-15b (miR-15b) on the expression of α-synuclein in SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP⁺)-induced injury and its role in the pathogenesis of Parkinson's disease (PD).Methods CCK-8 was used to determine the optimal concentration and time of MPP⁺ induction in the establishment of a PD cell model using SH-SY5Y cells, and then the PD cell model was transfected with the plasmids with overexpressed or silenced miR-15b. Real-time PCR and Western blot were used to measure the mRNA and protein expression of miR-15b and α-synuclein.Results SH-SY5Y cells had changes in cell morphology and a reduction in cell proliferation after MPP⁺ induction. There were significant reductions in the mRNA and protein expression of α-synuclein after miR-15b overexpression (P<0.05), and there were significant increases in the mRNA and protein expression of α-synuclein after miR-15b silencing (P<0.05).Conclusions MiR-15b can inhibit the mRNA and protein expression of α-synuclein in the PD cell model. MiR-15b may be involved in the enrichment and regulation of α-synuclein in the substantia nigra dopaminergic neurons in patients with PD.