Triple-negative breast cancer (TNBC) is a one of the subtypes of breast cancer which accounts for approximately10–20% of all breast cancers. LncRNA XIST (XIST) is reported to be dysfunctional in numerous tumortypes and is involved in the key pathways of cancer initiation, progression and metastasis. Thus, in the presentstudy, we explored the detailed molecular mechanism of XIST in TNBC. XIST was down-regulated in TNBCtissues and cell lines. Overexpressed XIST inhibited cell proliferation, epithelial mesenchymal transition(EMT) and induced apoptosis in vitro as well as suppressed TNBC tumor growth in vivo. MicroRNA (miR)-454 was up-regulated in TNBC tissues and cell lines. Knockdown of miR-454 inhibited TNBC progression bysuppressing cell proliferation, EMT and inducing cell apoptosis. Moreover, miR-454 was predicted andconfirmed to be a target of XIST, and rescue assay indicated that overexpressed miR-454 could reverse XISTrestoration mediated-anti-tumor effects on TNBC cells. In conclusion, XIST interacts with miR-454 to inhibitcells proliferation, EMT and induce apoptosis in TNBC, indicating a promising treatment strategy for TNBCpatients.