Recurrent implantation failure (RIF) affects up to 10% of in vitro fertilization (IVF) patients worldwide. However, the pathogenesis of RIF remains unclear. This study was aimed at identifying hub transcription factors (TFs) of RIF in bioinformatics approaches.The GSE111974 (mRNA), GSE71332 (miRNA), and GSE103465 (mRNA) datasets were downloaded from the Gene Expression Omnibus database from human endometrial tissue using R version 4.2.1 and used to identify differentially expressed TFs (DETFs), differentially expressed miRNAs, and differentially expressed genes for RIF, respectively. DETFs were subjected to functional enrichment analysis and the protein-protein interaction network analysis using the Search Tool for the Retrieval of Interacting Genes (version 11.5) database. Hub TFs were identified using the cytoHubb plug-in, after which a hub TF-miRNA-mRNA network was constructed using Cytoscape v3.8.2.Fifty-seven DETFs were identified, in which Gene Ontology analysis revealed to be mainly involved in the regulation of transcription. Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that DETFs were enriched in transcriptional misregulation in cancer, aldosterone synthesis and secretion, AMPK signaling pathway, and cGMP-PKG signaling pathway. EOMES, NKX2-1, and POU5F1 were identified as hub TFs, and a hub TF-miRNA-mRNA regulatory network was constructed using these three hub TFs, four miRNAs, and four genes.Collectively, we identified three promising molecular biomarkers for the diagnosis of RIF, which may further be potential therapeutic targets. This study provides novel insights into the molecular mechanisms underlying RIF. However, further experiments are required to verify these results.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.