Sepsis and its associated organ dysfunction syndrome is a leading cause of death in critically ill patients. Breast cancer susceptibility protein 1 (BRCA1)-associated protein 1 (BAP1) is a potential regulator in immune regulation and inflammatory responses. This study aims to investigate the function of BAP1 in sepsis-induced acute kidney injury (AKI). A mouse model with sepsis-induced AKI was induced by cecal ligation and puncture, and renal tubular epithelial cells (RTECs) were treated with lipopolysaccharide (LPS) to mimic an AKI condition in vitro. BAP1 was significantly poorly expressed in the kidney tissues of model mice and the LPS-treated RTECs. Artificial upregulation of BAP1 ameliorated the pathological changes, tissue injury and inflammatory responses in kidney tissues of the mice, and it reduced the LPS-induced injury and apoptosis of the RTECs. BAP1 was found to interact with BRCA1 and enhance stability of BRCA1 protein through deubiquitination modification. Further downregulation of BRCA1 activated the nuclear factor-kappa B (NF-κB) signaling pathway and blocked the protective roles of BAP1 in sepsis-induced AKI. In conclusion, this study demonstrates that BAP1 protects mice from sepsis-induced AKI through enhancing stability of BRCA1 protein and inactivating the NF-κB signaling. Display omitted •BAP1 is poorly expressed in renal tissues of neonatal mice with sepsis.•BAP1 overexpression alleviates sepsis-induced AKI in neonatal mice.•BAP1 overexpression alleviates LPS-induced injury in RTECs.•BAP1 enhances stability of BRCA1 protein through deubiquitination modification.•Downregulation of BRCA1 blocks the protective role of BAP1.