OBJECTIVE: To explore the mechanism of action of Citri Reticulatae Pericarpium-Pinelliae Rhizoma (CRP-PR) in treating gastric cancer (GC) by using pharmacology network. METHODS: Based on oral bioavailability and drug-likeness, the main active components of CRP-PR were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). DisGeNET Database was used to establish target databases for GC. Cytoscape software was used to construct a visual interactive network diagram of "Active Component-Target" and screen out the key targets. The STRING database was used to construct a protein interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the key targets. Additionally, TCGA and HPA databases were used for key target verification. RESULTS: Thirty-seven active components of CRP-PR were screened. The results of network analysis showed that the main components include 8-octadecenoic acid, stigmasterol, ferulic acid, and naringenin of the CRP-PR herb pair. The key targets of the PPI network mainly involved GAPDH, MAPK3, JUN, STAT3, GSK3B, SIRT1, ERBB2, and SMAD2. GO enrichment analysis involves 540 biological processes, 118 cellular components, and 171 molecular functions. CRP-PR components were predicted to exert their therapeutic effect on the tumor signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, and estrogen signaling pathway. The validation of the key genes in the TCGA and HPA database showed that most of the key target verification results were consistent with this article. CONCLUSION: CRP-PR can treat GC by mediating PI3K-Akt signal pathway, MAPK signal pathway, and other biological processes such as tumor cell proliferation, apoptosis, and vascular regeneration, which embodies the synergistic effect of multi-components, multi-targets, and multi-channels, and provides the theoretical basis and research ideas for further study of CRP-PR in treating GC. 8-octadecenoic acid, stigmasterol, ferulic acid, and naringenin may be the material basis for the treatment of GC.