Objective To analyze the material basis and potential mechanism of Yiqi Tiaofu decoction in the treatment of colorectal cancer (CRC) on the base of network pharmacology and molecular docking technology.Methods TCMSP and BATMAN-TCM databases were used to screen the active ingredients and potential targets of Yiqi Tiaofu decoction, while GeneCards, PharmGKB, TTD, and DrugBank platforms were used to retrieve the disease targets of CRC. The "component-target" network diagram was constructed using Cytoscape3.8.0 software, and the protein-protein interaction (PPI) analysis was performed using the STRING platform. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) enrichment analyses were conducted using R language data packages to predict its mechanism of action. Finally, the key active ingredients in Yiqi Tiaofu sdecoction and the core proteins in PPI were docked using AutoDock Vina and PyMol software for molecular validation.Results A total of 226 effective ingredients of Yiqi Tiaofu decoction were screened, involving 735 targets. In the "drug-component-target" diagram, 281 key active compounds were selected, and the PPI network they intervened in mainly involved core proteins such as STAT3, SRC, JUN, ESR1, TP53, MAPK3, MAPK1, RELA, FOS, and MYC. The results of GO and KEGG enrichment analyses showed that Yiqi Tiaofu decoction mainly intervened in various biological pathways such as xenobiotic stimulus response, nutrient level response, oxidative stress response, and lipopolysaccharide response, as well as related pathways such as the IL-17 signaling pathway, TNF signaling pathway, HIF-1 signaling pathway, and P53 signaling pathway in the treatment of chronic CRC. Molecular docking validation showed that quercetin had the best binding with the core target protein MAPK3, which was the target protein with the highest binding activity to the key chemical components of Yiqi Tiaofu Decoction.Conclusion Quercetin, luteolin, kaempferol, naringenin, nobiletin, acacetin, licochalcone A, isorhamnetin, 3'-methoxyglabridin and other key active ingredients in Yiqi Tiaofu decoction may act on STAT3, SRC, JUN, ESR1, TP53, MAPK3, MAPK1, RELA, FOS, MYC and other core target proteins, to exert pharmacological effects on CRC.