Esophageal squamous cell carcinoma (ESCC) is a common cancer in many developing countries in Asia and Africa, with a 5-year survival rate of approximately 20%. Most cases are diagnosed at an advanced age when there is no effective treatment strategy. Esophageal precancerous conditions have a much better prognosis, with a 5-year survival rate of over 90% by endoscopic diagnosis and treatment. Nevertheless, limitations, contraindications, and lymph node metastasis incompetency of endoscopy. Thus, the diagnosis and treatment of esophageal precancerous lesions remain a significant challenge. Biomarker investigations provide opportunities for target detection and therapy. Additionally, drug development is ongoing. Changes in lifestyle habits, such as diet balance, smoking and alcohol cessation, are beneficial for the prognosis of esophageal precancerous lesions. Collectively, multiple and sequential diagnoses and treatments are essential for curing esophageal precancerous lesions and reducing the incidence and mortality of ESCC.Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.