The higher expression of CD4+ (OS, hazard ratio [HR]= 0.395, P-value= 0.007) and CD4+ plus CD8+ (OS, HR= 0.478, P-value= 0.013) was positively correlated with better prognosis and survival, and also CD4+ (OS, HR= 0.317, P-value= 0.008) was an independent protective factor for ESCC patients. This evidence concerns the gene CD4 and esophageal squamous cell carcinoma.