The aim of this work was to identify the anticancer activity of Caryophyllene oxide (CPO) against MCF7 cell lines. CPO as phytochemical terpenoids is a chemoprevention derivative enhances breast cancer growth inhibition and proliferation. The cytotoxicity of CPO against breast cancer cells (MCF-7) was concentration dependent and the inhibitory concentration (IC50) of CPO was 24 µM/ ml. Also, toxicity of CPO was accompanied with the arrest of cell cycle significantly at the phase (G2/M) in compare with control. Also, the MCF-7 cells apoptotic profile showed a significant elevated Early and Late apoptosis and necrosis as well compared with control. In the meantime, DNA fragmentation detected via conduction of comet assay indicate elevated the percent of tail moment, tail DNA, and tail length versus control DNA fragmentation profile. In conclusion, Caryophyllene oxide is one of the most promising anticancer agents for breast cancer in worldwide.