Based on network pharmacology screening, this study for the first time discovered that Gomisin B might regulate the progression of CRC through the Toll-like receptor 4/Nuclear Factor-kappa B (TLR4/NF-κB) signaling pathway, and aimed to systematically reveal the molecular mechanisms by which YGS and Gomisin B inhibited the malignant phenotypes and immune escape of CRC cells. Here, TLR4 is linked to colorectal carcinoma.