Objective Use KEGG pathway and protein interaction network to screen the target genes of diastolic heart failure. Methods Using "Heart failure with preserved ejection fraction" as the key word, the Genecard database was searched for the disease target genes of diastolic heart failure, and the R language related data package was used to analyze the KEGG pathway to obtain the key pathways of diastolic heart failure and Key genes, upload genes on the STRING website, establish a protein interaction network of key genes, and screen out the core target genes of diastolic heart failure. Results A total of 526 diastolic heart failure genes were retrieved. Through KEGG enrichment analysis, 425 genes were enriched in 160 signaling pathways, mainly including PI3KAkt signaling pathway, JAK-STAT signaling pathway, etc., through protein interaction The core genes obtained from the network are VEGFA, AKT, IL6 and so on. Conclusion This study analyzed the critical signal pathways and core genes of diastolic heart failure through KEGG and protein interaction networks to provide a reference for further drug target research and basic experiments.