<h4>Introduction</h4>This study aims to systematically elucidate the association of adenosine deaminase with esophageal cancer from a genetic perspective and explore its potential underlying mechanisms and intervention strategies.<h4>Methods</h4>Through multi-level integrative analysis, two-sample Mendelian randomization analysis was performed, followed by serum validation in an independent case-control cohort. The gene discussed is ADA; the disease is esophageal cancer.