The use of traditional histopathological characteristics to classify esophageal squamous cell carcinoma (ESCC) has great limitations to guide clinical treatment. The establishment of molecular classification of ESCC is an inevitable requirement for precise treatment/personalized treatment. At present, the molecular classification of ESCC has not yet reached a consensus, nor has it been widely used in clinical practice. Many molecular markers ranging from protein level, gene polymorphism, DNA methylation to non-coding RNA are closely related to the occurrence, development, treatment response, prognosis and other biological behaviors of ESCC. It is expected to establish the molecular typing system of ESCC based on these molecular markers to better guide clinical practice.