Esophageal squamous cell carcinoma is the most common histological subtype of esophageal cancer. The carcinoma is more common in high-incidence areas such as in Central and Southeast Asia, Eastern and Southern Africa, South America, etc. Common risk factors associated with the cancer are tobacco smoking and excessive alcohol consumption. Dietary factors, genetic factors, microorganisms, and some other environmental factors may contribute to the etiopathogenesis of the disease. Despite the global incidence of esophageal squamous cell carcinoma decreases slightly in the recent years, esophageal squamous cell carcinoma is still a major cause of cancer-related morbidity and mortality worldwide. Further improvement of the outcomes of the patients with the disease could be achieved by early diagnosis, collaborative efforts of multidisciplinary clinical and research teams, use of standardized protocol for pathological reporting and staging of the disease, proper use of cancer tissue, as well as improvement in clinical, pathological, therapeutic, and research approaches to the cancer.