Clinical research found that TCM is therapeutic in treating gastric cancer. Clearing heat is the most common method, while some antirheumatic medicines are widely used in treatment as well. To explore the pharmacological mechanism, we researched the comparison between heat-clearing medicine and antirheumatic medicine in treating gastric cancer.First, related ingredients and targets were searched, respectively, and are shown in an active ingredient-target network. Combining the relevant targets of gastric cancer, we constructed a PPI network and MCODE network. Then, GO and KEGG enrichment analyses were conducted. Molecular docking experiments were performed to verify the affinity of targets and ligands. Finally, we analyzed the tumor immune infiltration on gene expression, somatic CNA, and clinical outcome.A total of 31 ingredients and 90 targets of heat-clearing medicine, 31 ingredients and 186 targets of antirheumatic medicine, and 12,155 targets of gastric cancer were collected. Antirheumatic medicine ranked the top in all the enrichment analyses. In the KEGG pathway, both types of medicines were related to pathways in cancer. In the KEGG map, AR, MMP2, ERBB2, and TP53 were the most crucial targets. Key targets and ligands were docked with low binding energy. Analysis of tumor immune infiltration showed that the expressions of AR and ERBB2 were correlated with the abundance of immune infiltration and made a difference in clinical outcomes.Quercetin is an important ingredient in both heat-clearing medicine and antirheumatic medicine. AR signaling pathway exists in both types of medicines. The mechanism of the antitumor effect in antirheumatic medicine was similar to trastuzumab, a targeted drug aimed at ERBB2. Both types of medicines were significant in tumor immune infiltration. The immunology of gastric tumor deserves further research.Copyright © 2022 Jiamin Xu et al.