Chrysin is a flavonoid possessing potential pharmacological activities against many diseases including cancer. Many studies have been reported on Chrysin showing anticancer activity against colon cancer. However, the mechanism with which Chrysin shows its anticancer activity is not known yet. Hence, the current study was framed to understand the molecular mechanism of Chrysin against colon cancer via gene set enrichment and network pharmacology analysis coupled with molecular docking study. Initially, Chrysin probable targets were identified by SwissTargetPrediction and their molecular pathway enrichment was analyzed by the STRING and KEGG pathway databases. The network among Chrysin, probable protein targets, and its pathways were constructed with the aid of Cytoscape 3.6.1v. Molecular docking was carried out with the aid of AutoDock Vina by PyRx 0.8v. Molecular dynamics was carried out by Schrodinger Desmond v6.1 software. Druggability, side effects, and ADMET analysis were determined using MolSoft, ADVERPred, and admetSAR2.0 web server, respectively. Chrysin potentially acts via metabolic pathways and Ras and PI3K-Akt signaling pathways associated with the progression of cancer. Among the probable targets, Chrysin exhibited the highest binding affinity against epidermal growth factor receptor comparable to standard molecule Erlotinib, and its root mean square deviation and interactions were found stable at 20 ns MD production run. Both Chrysin and Erlotinib shared common interactions with Asp831 active site residue and confirmed their potential antagonistic effect. In conclusion, Chrysin may serve as a potential anticancer small molecule in the future for the management and treatment of colon cancer.