Abstract: Objective The differentially expressed genes and pathways related to the occurrence and development of malignant peripheral nerve sheath tumours were screened by gene chip and bioinformatics analysis, so as to provide a new target and direction for the further study and treatment of malignant peripheral nerve sheath tumours. Methods The gene expression data set GSE66743, was downloaded from GEO database, and the differentially expressed gene was obtained by analyzing the gene expression of benign neurofibroma and malignant peripheral nerve sheath tumours. Subsequently, the DAVID database is used for GO function annotation and KEGG enrichment analysis. The String protein interaction database was used to construct the protein interaction network of DEGs and the Cytoscape software was used to identify the core genes from the protein interaction network. Finally, the core modules of the protein interaction network were screened by Cytoscape software and the KEGG enrichment analysis of the module design DEGs was carried out. Results a total of 493 up-regulated genes and 362 down-regulated genes were identified. GO analysis showed that DEGs was mainly involved in cell cycle, chromosome separation, mitotic cell cycle process, molecular function regulation and enzyme regulation activity. KEGG is mainly enriched in complement and coagulation cascade, proteoglycan, tyrosine metabolism, TNF signaling pathway and chemokine signaling pathway, cell cycle, protein digestion and absorption, ECM- receptor interaction and Fanconi anemia pathway. Ten core genes were screened by protein interaction network, and the enrichment analysis of the genes involved in the first three core modules showed that DEGs was mainly related to cell cycle, systemic lupus erythematosus, complement and coagulation cascade. Conclusion GO functional annotation and KEGG enrichment analysis reveal the potential pathogenesis of MPNSTs. The core genes and pathways provide potential diagnostic and therapeutic targets for malignant peripheral nerve sheath tumours.