Abstract <p>Transcription factors (TFs) are a group of proteins that regulate drought stress-responsive genes by binding to DNA at specific elements in promoter regions. No combinatorial analysis has been performed to identify the TFs and gene ontology (GO) involved in drought stress tolerance so far. Soybean microarray datasets were analyzed through R language packages. To identify TFs, sequences of down and up-regulated genes involved in drought stress tolerance using multiple promoter analysis was used. Common GO down and up-regulated genes were identified by Venny v2.1. Up-regulated key TFs were associated with AT-Hook, homeodomain, MYb/SANT, TBP, and WRKY and down-regulated key TFs related to Dof, bHLH, bZIP, and ZF-HD. Biological processes (BP) of up-regulated genes mainly belonged to fatty acid and photosynthesis processes and down-regulated genes mostly related to response to abiotic stresses. Molecular function (MF) of up-regulated genes mainly related to transferase enzymes and down-regulated genes mostly connected to regulators and inhibitory enzymes. Based on the results of this study, it is possible to understand the molecular mechanisms related to drought stress in soybean, and key TFs can be used to control the expression of genes related to drought stress in plant breeding and genetic engineering.</p>