In our study, 23 proteins, namely, ANXA1, hK8, CDKN1A, ABL1, SCAMP3, EGF, LYN, MetAP2, KLK13, ADAMTS15, hK14, VIM, TXLNA, GPC1, RSPO3, hK11, TRAIL, X5NT, CPE, FADD, TGFR2, SEZ6L and CD160, showed potential diagnostic utility for distinguishing early ESCC from controls and their serum levels showed a significant dose-response relationship with ESCC stages. This evidence concerns the gene KLK14 and esophageal squamous cell carcinoma.