Combined with the clinical stages of patients with ESCC, we found that the optimal model (p53, p62, HCCR, C‐myc, MDM2, miR‐21, miR‐223, miR‐375, and miR‐100) can provide higher diagnostic value for early ESCC, such as TNM0‐I, Tis‐T1, and no regional lymph node metastasis (N‐staging negative). Here, LETMD1 is linked to esophageal squamous cell carcinoma.