Parkinson's disease (PD) is a progressive and incurable neurodegenerative disorder. In this study, we utilized SHSY5Y cells an in vitro PD model to study the biological function of microRNA-505 (miR-505) in 1-methyl-4-phenylpyridinium (MPP+)-induced cytotoxicity. SHSY5Y cells were treated with MPP+ to induce PD-associated cell death and cytotoxicity. MiR-505 was found to be upregulated by MPP+. Lentiviral transduction mediated miR-505 downregulation protected SHSY5Y cells from MPP+ -induced cell death, whereas miR-505 upregulation had no effect on MPP+ -induced SHSY5Y cell death. MiR-505 downregulation also ameliorated MPP+ -induced cytotoxicity, by preserving MMP and reducing LDH level, caspase-3 and reactive oxygen species activities. Possible downstream target of miR-505, neural proliferation, differentiation and control 1 (NPDC1) was confirmed to be the downstream target of miR-505 in SHSY5Y cells. In addition, NPDC1 knockdown was shown to reverse the protection of miR-505-downregulation on MPP+ -induced cytotoxicity. Thus, our study demonstrated that miR-505, by inversely regulating NPDC1 may have a functional role in regulating human Parkinson's disease.