Breast cancer mortality still remains the second leading cause of cancer-related deaths worldwide. Patients with breast cancer have increasingly shown resistance and high toxicity to current chemotherapeutic drugs. This has led to the identification of newer drugs/therapies for treatment of breast cancer. Plant-derived products have proved to be an important source of anti-cancer drugs. Hence the present study was directed to evaluate the anti-cancer activity of ethanolic extract of the flowers of Annona squamosa and Manilkara zapota against MCF-7 breast cancer cell lines in vitro and was compared with the normal, Vero cell lines. At 3.12 μg/ml concentration of A. squamosa and M. zapota, MTT assay showed 74.6% and 82.6% cell viability respectively and at 100 μg/ml concentration of A. squamosa and M. zapota, MTT showed 1.3% and 2.6% cell viability respectively. The IC50 values were 6.87 μg/ml and 12.5 μg/ml for A. squamosa and M. zapota respectively. The results indicate that M. zapota flowers showed potent cytotoxic activity as compared to A. squamosa flower extract. The study confirms the anti-cancer activity of both the plant extracts and hence can be used to develop them as a novel drug for the management of breast cancer. Their property may be due to the presence of phytochemicals such as alkaloids, phenols and flavonoids.