Objective:To screen the key genes and signaling pathways in systemic sclerosis-related pulmo-nary arterial hypertension using bioinformatics methods.Methods:The microarray gene sets were downloaded from the GEO database,and the up-regulated differential genes were screened by R soft-ware and imported into DAVID and STRING databases for gene ontology(GO)functional annota-tion and KEGG signal pathway enrichment analysis.Cytoscape software was used to construct a pro-tein interaction network and screen key gene proteins.GSEA was used to explore the KEGG pathway and core genes associated with systemic sclerosis-related pulmonary arterial hypertension.Results:A total of 15 key gene proteins were screened out,and the key genes TLR4 and TNFSF10 were ob-tained by intersections with the genes reported in NCBI,OMIM,and GeneCards.There were 247 and 274 core genes of the two microarrays obtained from GSEA analysis,respectively,and core genes CTSG,PLAUR,and FCGR2A were screened.Conclusion:TLR4,TNFSF10,CTSG,PLAUR,and FCG2R may be closely related to the occurrence and development of systemic sclerosis-related pulmonary arterial hypertension and are expected to become potential targets for its early diag-nosis and precise treatment.