Background: Brain-specific angiogenesis inhibitor 1 (BAI1) which belongs to putative G-protein-coupled receptors (GPCRs), has been found down-expressed in various cancers and involved in cancer pathogenesis. However, the role and underlying mechanisms of BAI1 in triple negative breast cancer (TNBC) are still unclear. Methods: The expression levels of BAI1 in TNBC samples and cell lines were examined by immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting (WB). The functional effects of BAI1 on biological behaviors of TNBC cells were detected using plasmid and siRNA for BAI1 overexpression and knockdown, and the underlying mechanisms were investigated by Immunoprecipitation (IP), immunofluorescence (IF) and luciferase reporter assay. Results: BAI1 was downregulated in TNBC tissues and was significantly associated with poor disease-free survival. Functional experiments indicated that BAI1 inhibited cell proliferation and induced cell apoptosis and cell cycle arrest. Additionally, BAI1 overexpressed cells were more sensitive to cisplatin. Mechanistically, BAI1 interacted with MDM2, thereby enhanced p73 transcriptional activity, then promoted p21and BAX mRNA and protein expression. Overexpression of p73 abolished the BAI1 knockdown induced cell proliferation and the G2 phase cell population of TNBC, the sensitivity to cisplatin also rescued by overregulating p73 in BAI1 knockdown TNBC cells. Conclusions: Our results indicate that BAI1 is a promising prognostic factor in TNBC, and the expression of BAI1 inhibits cell proliferation and induces cell apoptosis and cell cycle arrest; Meanwhile, BAI1 increases the sensitivity of TNBC to cisplatin. For the underlying mechanism, BAI1 specifically binds to MDM2, and exerts its anti-tumor function by affecting the transcriptional activity of p73 protein, then inhibits the malignant progression of TNBC. The BAI1/MDM2/p73 axis may represent a potential target in the future research for TNBC.