Long-term recurrences or metastases occur in some patients with non-small cell lung carcinoma after complete remission in the early stages. This phenomenon may be related to the presence of tumor lesions undetectable by radiographic or laboratory methods, which are called minimal residual disease. Poor prognosis of patients is closely associated with these potential sources of tumor recurrences, so it is essential to supervise these lesions during the treatment of non-small cell lung carcinoma. Currently, the detection of minimal residual disease mainly relies on liquid biopsy, including circulating tumor DNA detection, circulating tumor cell detection and other approaches. Through non-invasive detection methods, remaining tumor lesions provide us with the progression of the tumor and specific molecular information, predict the prognosis of patients, and further guide the follow-up treatment regimen. In this review, we will explore the mechanism and impact of the occurrence and development of minimal residual disease, and focus on its potential application value in the clinical treatment process.