Background: At present, Mangrove plants have gained importance in drug discovery due to the presence of many phytomolecules of medicinal importance. Excoecaria agallocha is widely distributed medicinal mangrove which has been traditionally used to treat sores, ulcers, and leprosy. Objective: The aim of the present study is to analyze the cytotoxic potential of Exoecaria agallocha leaves in terms of its antiproliferative activity, apoptosis induction, and cell cycle arrest in the breast cancer MCF-7 cell lines. Materials and Methods: The ant proliferative nature of the EEEA extract was determined by direct microscopic observation as well as 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay by employing the different concentrations of the plant extract, and the IC50 values were calculated. Apoptosis-inducing potential was determined by double staining with acridine orange/ethidium bromide staining method and further confirmed by annexin V staining. Flow cytometry was performed with IC50 concentration of EEEA drug treated MCF-7 cells to determine arresting stage in the cell cycle progression. Results: There was a significant cytotoxic activity exhibited by the ethanolic extract of E. agallocha leaves (EEEA) in the direct microscopic as well as MTT assay with IC50 value of 56.5 μg/ml. Well prominent fluorescent microscopic images of morphological changes in the double staining method indicate the apoptotic potential of the extract which was further confirmed by annexin V staining. Suppression of cell cycle progression at subG1 and G1/G2 phases were also evidenced in the flow cytometry analysis. Conclusion: From the above results, it may be concluded that the ethanolic leaf extract of E. agallocha (EEEA)-induced apoptosis mediated cytotoxic and antiproliferative activity in the breast cancer MCF-7 cell lines which can be developed into a new drug for treating breast cancer.