Herein, we conducted an analysis of TP53 mutation and p53 protein expression in two-large ESCC cohorts, using a series of methods including whole-genome sequencing (WGS), whole exon sequencing (WES), regionally targeted sequencing (TRS) and IHC, to further clarify the association between TP53 mutation status/ the expression of p53 protein and clinicopathologic phenotype and prognosis. The gene discussed is TP53; the disease is esophageal squamous cell carcinoma.