Among different pathological types and TNM stages, the highest positive rate of SHOX2 gene methylation was found in patients with adenocarcinoma and TNM stage IV LC (P < 0.05); the comparison of the positive rate of SHOX2 gene methylation among patients with different ages, genders, smoking histories or not, and patients with different histologic differentiation, maximum tumor diameter, and lymph node metastasis showed no statistically significant difference (P > 0.05). The gene discussed is SHOX2; the disease is laryngotracheoesophageal cleft.