AIM: In this study, bioinformatics technology was used to explore the differentially expressed genes in antibody-mediated rejection after renal transplantation, and to screen out the possible mechanisms and potential therapeutic targets of AMR-related miRNAs after renal transplantation, in order to provide new idea for the targeted therapy of AMR after transplantation. METHODS: The dataset GSE115816 was downloaded from the GEO database, and the differential expression of miRNAs in stable renal transplantation (SGF) group and the antibody-mediated rejection (AMR) group after renal transplantation was analyzed online by using DESeq 2R software. TargetScan software predicted the related targets of miRNAs, and the differentially expressed genes (DEGs) were analyzed through through gene ontology (GO) enrichment analysis and Kyoto gene and genome encyclopedia (KEGG) enrichment analysis, then key genes were screened by String database and Cytoscape, and finally verified by TargetScan online analysis. RESULTS: A total of 10 differentially expressed miRNAs were identified in the AMR group by comparison with the SGF group, with the most significant difference in expression of miR-144-5p. A total of 143 miR-144-5p related targets were predicted by Targetscan software. GO analysis showed that DEGs were mainly involved in angiogenesis, synaptic signaling, and transcriptional co-activator regulation. KEGG analysis showed that DEGs were mainly enriched in the thyroid hormone signaling pathway, human papillomavirus infection, and PI3K-AKT signaling pathway. The 10 Hug genes were screened by PPI network. Based on the 6 algorithms in cytoHubba, 5 key genes were obtained by taking the intersection of the top 10 Hug genes of each algorithm, which were NCOA2, NCOA1, FOXO1, PAX3, and PPARGC1A. After the literature review, we found that FoxO1 plays an essential role in immune system diseases and kidney diseases. In our study, we chose FoxO1 as a potential target protein for miR-144-5p. Finally, TargetScan online analysis showed that miR-144-5p has a targeted binding site with the 3' UTR region of FoxO1. CONCLUSION: MiR-144-5p plays an important role in AMR after Kidney transplantation. MiR-144-5p targeting FoxO1 may be a potential therapeutic target and prognostic biomarker for AMR.