Background and objective: Colon cancer is increasing in people recently and ginger (Zingiber officinale), as a commonly used herbal medicine, has been suggested as a potential agent against colon cancer. This study was aimed to identify the bioactive compounds and potential mechanisms of ginger for colon cancer prevention by an integrated network pharmacology approach.Methods: Putative ingredients of ginger and its related targets were discerned from the TCMSP database. After that, the targets interacting with colon cancer were collected using Genecards, OMIM, and Drugbank databases. KEGG pathway and GO enrichment analysis were performed to explore the signaling pathways related to ginger for colon cancer treatments. The PPI and compound-target-disease networks were constructed using Cytoscape.Results: Six potential active compounds, 285 interacting targets in addition to 1356 disease-related targets were collected, of which 118 intersection targets were obtained. A total of 34 key targets including PIK3CA, SRC, and TP53 were identified. These targets were mainly focused on the biological processes of phosphatidylinositol 3-kinase signaling, cellular response to oxidative stress, and cellular response to peptide hormone stimulus. The KEGG enrichment manifested that three signaling pathways were closely related to colon cancer prevention of ginger, including cancer, endocrine resistance, and hepatitis B pathways. TP53, HSP90AA1, MAPK8, JAK2, CASP3, and ERBB2 were viewed as the most important genes, which were validated by molecular docking simulation.Conclusion: This study demonstrated that ginger produced preventive effects against colon cancer by regulating multi-target and multi-pathway with multi-components. And, the combined data provide novel insight for ginger compounds developed as new drug for anti-colon cancer.