This study shows that autoantibodies against STIP1 have sensitivities of 35.7% (95% CI: 22.0–52.0%) in the training cohort and 38.5% (95% CI: 15.1%–67.7%) in the validation cohort to diagnose early-stage ESCC. The gene discussed is STIP1; the disease is esophageal squamous cell carcinoma.