To clarify the expression level and methylation level of esophageal cancer related gene 4 in laryngeal malignant tumor and tumor adjacent tissues, and to explore its potential correlation with the clinicopathological characteristics of patients with laryngeal cancer is the objective of the study. The clinical samples were collected from 20 patients with primary laryngeal cancer in Xiangtan Central Hospital from December 2017 to December 2018. The level of expression and methylation of esophageal cancer related gene 4 in the samples were detected by the next-generation sequencing technology. In 15 cases, the messenger ribonucleic acid expression of esophageal cancer related gene 4 of tumor was significantly lower than that in adjacent tissues (p<0.05). In 18 cases, the methylation level of esophageal cancer related gene 4 in tissue of laryngeal squamous carcinoma was 46.7 %, which was significantly higher than that in adjacent tissues (26.2 %, p<0.01). Combined with clinical data analysis, it was found that, in laryngeal high and middle differentiated squamous cell carcinoma, the expression level of esophageal cancer related gene 4 was low and the methylation level was significantly increased. However, the expression of esophageal cancer related gene 4 in small round cell carcinoma was high, while the methylation level was significantly reduced. Smoking and drinking habits are the related factors of laryngeal high and middle differentiated squamous cell carcinoma. These results indicated significant difference of the esophageal cancer related gene 4 expression and methylation level between laryngeal malignant tumor and tumor adjacent tissues. Furthermore, the correlation between esophageal cancer related gene 4 expression and methylation level in laryngeal malignant cancer was found. Esophageal cancer related gene 4 could be regarded as a potential therapeutic target gene for laryngeal malignant cancer.