Abstract: Objective To explore the effect of long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) on Parkinson's disease (PD). Methods PD models in vivo and in vitro were established. Mice behavioral changes were detected by pole and rota-rod test. Cell viability and apoptosis of SH-SY5Y cells were determined by MTT assay and flow cytometry, respectively. Dual luciferase reporter gene assay, real-time fluorescence quantitative PCR (qRT-PCR), Western blot and immunohistochemistry were performed to investigate the effect of XIST on PD. Results XIST expression was upregulated, but miR-15b-5p expression was downregulated in PD model. Silencing XIST (si-XIST) could shorten the time for mice to prepare for crawling down the pole and prolong the retention time. In addition, si-XIST also increased the number of tyrosine hydroxylase positive (TH⁺) neurons. miR-5b-5p was the target gene of XIST. Conclusions si-XIST can inhibit autophagy and apoptosis in PD model by regulating miR-15b-5p.