Objective:To explore the potential target and signaling pathway of Sijunzi Decoction in treating Colorectal Cancer (CRC) with network pharmacology.Methods:The Traditional Chinese Medicine System Platform (TCMSP) and Swiss Target Prediction database were adopted to establish the database of Sijunzi Decoction effective ingredients and targets. Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man, Drugbank and GeneCards were used to build the CRC target database. The common gene names of target proteins were checked in Uniprot database. The STRING database was applied to analyze the interactions between the targets and the DAVID was used for the enrichment analysis on gene ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The network topology results were analyzed by Cytoscape 3.7.1 software.Results:134 active compounds of Sijunzi Decoction were gained, and PPI includes 125 targets protein (TP53,AKT1,IL-6,et al.). The 516 cellular biological processes, 53 cellular component and 98 molecular function were obtained through GO biological process enrichment analysis. The result of KEGG pathway enrichment showed that PI3K-Akt signaling pathway, TNF signaling pathway and FoxO signaling pathway were the main pathways.Conclusion:Sijunzi Decoction is mainly used to treat CRC by regulating key proteins such as TP53,AKT1, IL-6 and interfering with signal pathways such as PI3K-Akt, TNF and FoxO, reflecting the characteristics of Sijunzi Decoction in the treatment of CRC with multi-component,multi-target and multi-pathway characters.