〔Abstract〕 Objective To explore the effects of piperlongumine(PL) on the proliferation and apoptosis of triple-negative breast cancer MDA-MB-231 cellsin vitroandin vivoas well as its possible molecular mechanism. Methods MDA-MB-231 cells were treated with different concentrations of PL. MTT assay was performed to detect the level of cell proliferation. The apoptotic level was detected by flow cytometry. Western blot was performed to detect protein expression levels of proliferating cell nuclear antigen(PCNA), B-cell lymphoma-2(Bcl-2), cyclin-dependent kinase inhibitor 1A(CDKN1A/p21), phosphorylated signal transducer and activator of transcription 3(p-STAT3), signal transducer and activator of transcription 3(STAT3), hypoxia inducible factor-1α(HIF-1α) and Survivin. MDA-MB-231 cells were used to model tumor bearing nude mice and then PL was injected by intraperitoneal(i.p.). The tumor protein expression levels of PCNA, p-STAT3, STAT3, HIF-1α and Survivin were detected by Western blot. Results PL inhibited cell proliferation and induced apoptosis in a dose-dependent manner. PL down-regulated the protein expression levels of PCNA, Bcl-2, p-STAT3, HIF-1α and Survivin, and up-regulated the protein expression level of p21. Furthermore, PL inhibited tumor growth and down-regulated the protein expression levels of PCNA, p-STAT3, HIF-1α and Survivin in nude mice. Conclusion PL inhibits the proliferation of MDA-MB-231 cellsin vitroandin vivo, and the underlying mechanism can be related to the negative regulation of STAT3/HIF-1α pathway.