Abstract: ob＜x＞jective This study aimed to explore the effect of lncRNA XIST on Parkinson’s disease (PD). Methods In our study, PD models in vivo and in vitro were established. Mice behavioral changes were detected by pole and rota-rod test. SH-SY5Y cells viability, apoptosis was detected by MTT assay and flow cytometry, respectively. Dual luciferase reporter gene assay, qRT-PCR, Western blot and immunohistochemistry were performed to investigate the molecular mechanism of XIST in PD. Results The ex＜x＞pression of XIST was upregulated in MPTP-induced brain tissue and dopamine neurons, and MPP+-induced SH-SY5Y cells, but the ex＜x＞pression of miR-15b-5p was downregualted. Silencing XIST could decrease the T-turn and T-descend time, and increase the retention time. Moreover, silencing XIST could also increase TH positive neurous. miR-15b-5p was the target gene of XIST. si-XIST inhibited MPP+ induced SH-SY5Y cell apoptosis and autophagy by regulating miR-15b-5p. Conclusion si-BDNF-AS could inhibit autophagy and apoptosis in MPTP-induced PD through regulating miR-15b-5p.