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Background: The aim of this study was to investigate the effect of carnosol, a naturally occurring polyphenol found in rosemary, on the viability, migration, invasion, and tumour growth of the triple-negative human breast cancer cell line MDA-MB-231. Methods: Antiproliferative effects of carnosol were measured with a cell viability kit (Millipore). Autophagy was determined by transmission electronic microscopy, acidic vesicular formation, and increased accumulation of LC3-II. Apoptosis was assessed by annexin V, caspase 3, 8 and 9, and PARP cleavage. Wound-healing assay and invasion matrigel assays were used to assess the anti-migration and anti-invasion potential of carnosol. MMP-9 activity was measured using gelatin zymography. A chick embryo chorioallantoic tumour growth assay was used for in vivo tumour growth and metastasis experiments. Findings: Carnosol was able to inhibit the viability of the MDA-MB-231 cells in a time- and dose- dependent manner and induce G2 cell cycle arrest. Carnosol induced autophagy followed by apoptotic cell death in the MDA-MB-231 cell lines. Carnosol induced a dose-dependent accumulation of reactive oxygen species. Abrogation of reactive oxygen species by tiron, a reactive oxygen species scavenger, dramatically reduced both apoptosis and autophagy. Carnosol treated-cells exhibited histone H3 and H4 hypoacetylation associated with downregulation of two histone acetyl transferases, p300 and PCAF. Furthermore, non-cytotoxic concentrations of carnosol significantly inhibited the migration and invasion of MDA-MB-231 cells and decreased the activities of matrix metalloproteinase-9. Carnosol inhibited tumour growth and metastasis in vivo. Carnosol targeted pSTAT3, TNF-α, and DAPK. Interpretation: Carnosol exerts its anti-breast cancer effects through multiple targets, including histone modifications, autophagy, and apoptosis. Hence, carnosol has potential to be a new anticancer drug against breast cancer. [ABSTRACT FROM AUTHOR]