The compound 8-prenylnaringenin (8-PN) is a prenylflavonoid that can be isolated from hops and beer and has anti-cancer properties against breast cancer. The aim of this study is to investigate the anti-proliferative and apoptotic activities of 8-PN against human colon cancer HCT-116 cells.Colon cancer HCT-116 cells were treated with 8-PN and subjected to MTT and acridine orange/propidium iodide (AO/PI) staining to investigate the cytotoxicity of 8-PN. Arrest of the cells at different phases of cell cycle was monitored in the presence of 8-PN. Moreover, the apoptotic effects of 8-PN was assessed via annexin V and caspase activity assays and compared to the untreated cells.The findings showed that 8-PN revealed strong inhibitory effect against HCT-116 cells with an IC value of 23.83 ± 2.9 μg/ml after 48 h. However, at similar concentrations and experimental time-points, the compound did not show cytotoxic effect to non-cancerous colon cells (CCD-41). Annexin-V assay indicates that 38.5% and 14.4% of HCT-116 cells had entered early and late stages of apoptosis, respectively after exposure of the cells to 8-PN for 48 h. Caspase activity assay illustrates that apoptosis is activated through both intrinsic and extrinsic pathways. Moreover, flow cytometry cell cycle results indicate that treatment with 8-PN significantly arrested the HCT-116 cells at G0/G1 phase.These findings reveal that 8-PN has anti-proliferative activity against HCT-116 colon cancer cells via induction of intrinsic and extrinsic pathway-mediated apoptosis. Further investigations should be carried out to unravel the mechanistic pathways underlying these activities.