Colorectal cancer is considered one of the most occurring cancers leading to death. Apoptosis is defined as a programmed cell death controlled by different gene families via intrinsic and extrinsic pathways. Soybean and black seed have been found to possess anti-proliferative, anticancer, and anti-chemo-resistant properties. In this study, we assessed the preventive impact of soybean and black seed extracts different concentrations and their mixture against HT-29 colon cancer cell line through apoptosis using flow cytometry, DNA fragmentation assays and expression of six genes related to apoptosis. Flow cytometry analysis of the mixture of soybean and black seed extracts showed the highest total apoptosis (early and late apoptosis) and low necrosis percentages when compared to cisplatin and black seed extract at IC50. DNA fragmentation increased significantly among the groups treated with the mixture of the extracts with the highest fragmentation percentage. Expression analysis revealed a significant downregulation of P53, BIRC5, BCL2L1 and XIAP genes and a significant upregulation of Bax genes. Whereas FAS gene was expressed without any significant difference in all groups compared to control. The mixture demonstrated the most significant difference in each gene among the groups. As a result, mixture exhibited pro-apoptotic effect through different analyses.