The detection of minimal residual lesions represented by circulating tumor DNA can detect residual cancer lesions that cannot be displayed by traditional imaging in advance. The positive status and dynamic changes are closely related to the prognosis evaluation of various solid tumors, the effectiveness of neoadjuvant therapy, the prediction of postoperative recurrence risk, and the precise implementation of adjuvant therapy. This article summarizes the advantages and challenges faced by the application of circulating tumor DNA testing in individualized multidisciplinary diagnosis and treatment of esophageal cancer, in order to better carry out precise diagnosis and treatment of esophageal cancer under the guidance of minimal residual lesion detection.