The use of plants as a source of palliative or treatment for cancer is quite widespread worldwide. Annona muricata L. (Graviola) exhibits a wide array of ethno-medicinal and curative properties, accredited to different plant organs. The bio-activity of this plant is characterized by the production of secondary metabolites like alkaloids, phenols and most importantly annonaceous acetogenins found uniquely in this plant group. While A. muricata is gaining recognition as anti-cancer treating plant, the present study was undertaken to affirm probable genotoxic effect of pulp and leaf hydro-methanolic extracts in comparison with potent acetogenin, Annonacin on DNA of breast cancer (MCF-7) cells using alkaline comet assay. Genotoxic effects were evaluated using single cell gel electrophoresis (SCGE) method and the tail parameters from pooled comets were scored using TriTek CometScore Pro ver. 1.01.44 software. The average tail length (TL), percentage of tail DNA (TD), tail moment (TM) and Olive tail moment (OTM) were calculated which indicates the extent of DNA damage in cells followed by Statistical analysis. Study revealed the highest DNA damage toward MCF-7 cells in the form of comet streak or tails in 0.01 mg/mL Annonacin treatment. While the leaf extracts of A. muricata showed significantly higher tail parameters than the pulp extract in relation to untreated control. Our findings indicated that among the two extracts from A. muricata tested, the leaf exhibited better genotoxic potential compared to pulp extract, however, the plant extracts showed lesser efficacy in comparison with standard annonacin compound. Thus, this study further calls for more methodical safety evaluation and other end-points of genotoxicity apart from DNA damage.