Abstract：Objective：To investigate the effect and molecular mechanism of anisodamine(Ani) on MPP+-induced SK-NSH cell damage. Methods：SK-N-SH cells were divided into Con group， MPP+ group，MPP++Ani-L、M、H group， MPP++ si-NC group， MPP++si-LINC00657 group， MPP++Ani+pcDNA group， MPP++Ani+pcDNA-LINC00657 group. Kit to detect malondialdehyde(MDA) content and glutathione(GSH) activity，flow cytometry to detect apoptosis，Western blot method to detect Bcl- 2 and Bax protein expression，real- time fluorescence quantitative PCR(RT- qPCR) detection of LINC00657 and miR- 496 expression， dual luciferase report test to detect the targeting relationship between LINC00657 and miR- 496. Results：After treatment with anisodamine at different concentrations， MDA content was decreased in MPP+-induced SKN- SH cell， GSH activity was increased， apoptosis rate was decreased， Bcl-2 expression was increased， Bax expression was decreased， LINC00657 expression was decreased， expression of miR- 496 was increased， in a concentrationdependent manner(P＜0.05). LINC00657 regulates the expression of miR-496， after inhibiting the expression of LINC00657， MDA content was decreased in MPP+-induced SK-N-SH cell， GSH activity was increased， apoptosis rate was decreased， Bcl-2 expression was increased， Bax expression was decreased(P＜0.05). LINC00657 overexpression reversed the effect of anisodamine on MPP +- induced SK- N- SH cell damage. Conclusion： Anisodamine protects SK- N- SH cells from MPP +- induced injury by regulating the lncRNA LINC00657/miR-496 pathway.