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Introduction: Gastric cancer is a multifactorial disease and the fourth most common cancer in the world and the second cause of death from cancer. This study was designed and performed to investigate CDH1 and RUNX3 genes expression in healthy and tumor marginal tissue of people with gastric cancer. Methods: In this case-control study, 64 samples including 32 samples of gastric tumor tissue and 32 samples of normal tissue from the patientchr('39')s were prepared. Next, RNA was extracted from tissue and cDNA was made. Finally, using Real Time Polymerase Chain Reaction (PCR), gene expression measurements were also performed for CDH1 and RUNX3. Paired t test was used for data analysis. Result: Overall, in 87.5% of patients with gastric cancer, CDH1 margin dropped to 7.35 in tumor tissue compared to healthy tissue gene expression, and in 90% of patients, RUNX3 gene expression was reduced by as much as 46.5 times. Significant differences were found between normal and cancerous cells of these patients. Conclusions: Given the role of RUNX3 gene, CDH1 and decreased expression of tumor suppressor genes as they are significantly in tumor tissue of patients with gastric cancer is justified.