Given the close relationship between S100A8/A9, SAA1, ENO1, TPI1, PGAM1 and tumor, with our present data, we were committed to developing a biomarker panel consisting of these six proteins for early detection of ESCC patients, which have yielded high specificity and sensitivity of 0.906 and 0.967, and AUC up to 0.945, higher than each of them alone, suggesting the synergistic effects and increased diagnostic efficacy of these six biomarkers as a potential biomarker panel. Here, ENO1 is linked to esophageal squamous cell carcinoma.