The results suggest that vitexin and aspirin can regulate the PI3K-Akt signaling pathway, IL17 signaling pathway, TNF signaling pathway, and NF-κB signaling pathway through multiple target proteins such as NFKB1, PTGS2, MAPK1, MAPK3, and TP53, reflecting the characteristics of the new combination of vitexin and aspirin through multi-targets and multi-pathways, which echoes the complex pathogenesis of colorectal cancer. Here, NFKB1 is linked to colorectal cancer.