Objective:To analyze the data of ultra-high dose rate (FLASH) radiotherapy in GEO (Gene Expression Omnibus) database by bioinformatics method, in order to find the hub genes involved in flash radiotherapy induced acute T-lymphoblastic leukemia.Methods:The gene expression profiles of malignant tumors receiving FLASH radiotherapy were downloaded from GEO database. The R software was used to screen the differential expressed genes (DEGs) and analyze their biological functions and signal pathways. The protein-protein interaction (PPI) network of DEGs was analyzed by online tool of STRING, and Hub genes were screened by Cytoscape plug-in. The expressions of screened Hub genes in acute T lymphoblastic leukemia were identified with TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) database.Results:Based on the analysis of GSE100718 microarray dataset of GEO database, a total of 12 800 genes were found to be associated with radiosensitivity of acute T lymphoblastic leukemia, of which 61 significantly altered DEGs were selected for further analysis. It was found that these genes were involved in the biological processes of metabolism, stress response, and immune response through the pathways of oxidative phosphorylation, unfolded protein response, fatty acid metabolism, and so on. PPI analysis indicated that HSPA5 and SCD belonged to the Hub genes involved in the regulation of FLASH radiosensitivity, and they were significantly highly expressed in acute T lymphoblastic leukemia combined with TRD/LMO2-fusion gene.Conclusions:Through bioinformatics analysis, the Hub genes involved in regulating the sensitivity of FLASH radiotherapy and conventional radiotherapy can be effectively screened, and thus the gene expression profiles can be used to guide the stratification of cancer patients to achieve a precise radiotherapy.