This paper reviews the efforts and achievements of Chinese scientists in studying the pathogenesis, molecular mechanism, and early diagnosis and treatment of esophageal squamous cell carcinoma (ESCC) based on our work. It is suggested that: (1) ESCC is a typical multifactorial disease, and it is very important to protect the esophagus from various physical and chemical injuries to prevent the development of this malignancy; (2) based on a variety of omics studies, it is necessary to adopt a high-quality prospective population study design, integrate existing results to carry out systematic analysis, and explore potential intervention targets in depth; and (3) in the absence of high attributable risk factors, large-scale screening needs to be evaluated in randomized controlled studies to evaluate its effects and health economic value, and at the same time, existing screening models need to be further improved with regard to precision and individualization.