With the development of molecular biological markers, more and more tumor markers are used in the clinic. For postoperative follow-up of patients with differentiated thyroid cancer (DTC), thyroglobulin (Tg) is the most critical serum marker. Rational application of tumor marker Tg to improve the sensitivity and specificity of diagnosis is of great value for postoperative follow-up and prognostic assessment of DTC patients, and helps to achieve better management of DTC. Tg is a group of functional glycoprotein complexes in thyroid follicular cells, whose physiological function is mainly the iodinated synthesis of thyroid hormones, and whose physiological activity is stimulated by thyroid stimulating hormone (TSH), a small fraction of which can be detected in the blood circulation under physiological conditions. The main causes of elevated serum Tg in patients are benign thyroid disease and malignant thyroid disease, of which the former includes destruction of thyroid follicles, hyperfunction, and the effects of drugs and special foods, and the latter mainly refers to differentiated thyroid cancer (DTC), which mainly includes proliferation of DTC cells, metastasis, and short-term destruction and apoptosis after treatment with radioactive iodine 131I, etc. However, when normal thyroid tissue is completely removed (clear nail), DTC cell activity release is the only source of Tg. At this time, if Tg is detected in the serum, it often indicates residual DTC lesions or recurrence. Tg is the main judgment index for judging the efficacy and dynamic monitoring of DTC patients after nail clearing treatment, and it is an important judgment basis for disease course monitoring, follow-up effect assessment and prognosis diagnosis of DTC. According to the current domestic and international guidelines on thyroid cancer treatment, the diagnosis and follow-up of DTC patients after surgical treatment as well as radioactive 131I (RAI, nail clearing) treatment and thyroid hormone replacement suppression (also called TSH suppression) treatment mainly rely on serum Tg test and other imaging examinations such as ultrasound. Patients with DTC should undergo regular and long-term serum Tg testing to facilitate timely detection of lesion recurrence, metastasis or/and objective and effective evaluation of relevant follow-up treatment and prognostic judgment. Clinicians can understand the disease progression and tumor load of patients after total thyroidectomy through continuous dynamic monitoring of Tg. Studies have confirmed that serum Tg has the highest diagnostic sensitivity and specificity for determining residual or recurrent DTC in patients with DTC after thyroid surgery and combined with RAI therapy (clear nail), after TSH stimulation (TSH > 30 mIU/L) and without interference from anti-thyroglobulin autoantibodies (TgAb). In addition, it is important to improve the sensitivity of Tg assay when serum Tg is used clinically for DTC detection. High-sensitivity Tg assay helps to detect micro-metastases in postoperative patients with DTC at an early stage, and with further increase in the sensitivity of serum Tg assay, it is expected that more patients with DTC may be definitively excluded from residual lesions or detected with residual, recurrent or metastatic lesions earlier.