We found that 66.5% of 1073 ESCC samples had non‐silent SNV of TP53, resulting in a highest level of CCA of TP53 gene, and the proportion of three SBS signatures (SBS1*, SBS5*, and SBS18*) was higher, followed by SBS15*. The gene discussed is TP53; the disease is esophageal squamous cell carcinoma.