Background: Ficus hispida Linn. (Family Moraceae), well-known beneficial medicinal shrub, has been traditionally used for the treatment of various diseases such as leukoderma. Objective: The aim of the present study is to investigate the efficacy of F. hispida ethanolic leaves extract for antiproliferative, apoptotic, cell cycle blockade, and wound healing. Materials and Methods: F. hispida leaves extract was treated with colorectal adenocarcinoma cancer cell line HT29 for 24 h with control. The cells were treated at varying concentration ranges of 15, 31, 62, 125, and 250 μg/ml each The cytotoxicity effect of leaves extract was studied by 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide assay and their anticancer activity was further evaluated using cell cycle analysis and wound scratch assay. Results: The end antiproliferative result showed that HT-29 cell viability decreases in a concentration-dependent manner and the growth inhibitory effect (IC50) values are obtained at a concentration of 125 μg. The increase in number of apoptotic cell was observed after treating HT-29 cells with the sample in double-staining methods. G0/G1 phase of the cell cycle was significantly blocked by the test sample followed by the G2/M phase in a negligible manner. In vitro cell wound closure or contracture was not significant when compared the sample against control group. Conclusion: F. hispida Linn. ethanolic leaves extract had shown to possess excellent cytotoxic effect through inducing apoptosis, especially causing cell cycle arrest at the G0/G1 phase.