<p>The objective of this article is to explore the influence and process by which periodontitis affects the metastasis of gastric cancer cells. Human gingival fibroblasts (HGFs) underwent stimulation with lipopolysaccharide (LPS), and ELISA was used to detect inflammatory factor expression. Using cell co-culture technology, the effect of HGFs on the migration of gastric cancer cells was observed. CCK8, qPCR, Western blot, RNAi, Cell scratch and transwell were used to analyze the relationship between CXCL12/CXCR4, Snail2 and EMT, and their effects on cancer cell migration. The results showed that CXCL12 levels rise in periodontitis and gastric cancer. HGFs can promote the migration of gastric cancer cells. CXCL12 also boosts Snail2 expression in gastric cancer cells. AMD3100 and si-CXCR4 can significantly inhibit the expression of Snail2. Moreover, CXCL12 can promote EMT, while si-Snail2 and si-CXCR4 significantly reduced the upregulation trend of N-cadherin and Vimentin expression, and reverses the downregulation trend of E-cadherin expression. CXCL12 can promote the migration of gastric cancer cells, while the migration rates of gastric cancer cells are notably reduced after AMD3100, si-CXCR4 or si-Snail2 intervention. In summary,&#xa0;the CXCL12/CXCR4-Salil2-EMT signaling pathway is involved in the migration of gastric cancer cells promoted by periodontitis. This will uncover new insights into the mechanisms that might play a role in the development of gastric cancer and strategies for targeted therapy.</p>