<p>Gastric cancer is a common digestive system malignancy worldwide, and its high metastatic potential is one of the main reasons for poor patient prognosis. Dihydrocapsaicin, a natural derivative of capsaicin found in chili peppers, has recently been shown to possess anti-tumor potential. However, the effects and underlying mechanisms of dihydrocapsaicin on gastric cancer cell migration and invasion remain unclear. This study aims to investigate the impact of dihydrocapsaicin on the migratory and invasive abilities of gastric cancer cells and to elucidate the regulatory role of TRPV1 in this process. Human gastric cancer cell lines NCI-N87 and HGC-27 were treated with different concentrations of dihydrocapsaicin. The changes in the migration and invasion abilities of gastric cancer cells were detected. Meanwhile, WB was used to detect the differential expression of TRPV1, E-cadherin, N-cadherin, Vimentin, and Snail. Subsequently, the expression of TRPV1 was interfered in the dihydrocapsaicin-treated gastric cancer cell lines, and the differential expressions of the above cell migration, invasion, and E-cadherin, N-cadherin, Vimentin, and Snail proteins were detected. Dihydrocapsaicin could significantly and dose-dependently inhibit the migration and invasion of gastric cancer cells NCI-N87 and HGC-27. In addition, dihydrocapsaicin treatment significantly increased the expression of TRPV1 and E-cadherin proteins in gastric cancer cells, and significantly inhibited the expression of N-cadherin, Vimentin, and Snail proteins in gastric cancer cells. Functional rescue experiments confirmed that when the expression of TRPV1 was inhibited, the inhibitory effect of dihydrocapsaicin on the migration and invasion of gastric cancer cells was significantly weakened. Dihydrocapsaicin can effectively inhibit the migration and invasion abilities of gastric cancer cells by upregulating the expression of TRPV1.</p>