Abstract: The incidence of differentiated thyroid carcinoma (DTC) has kept increasing over the recent decades, and most patients carry a good prognosis and long-term survival through surgery, radioactive iodine therapy, and thyroid-stimulating hormone suppression therapy, while some patients have persistent, recurrent or metastatic disease. Thyroglobulin (Tg) can be regarded as a sensitive and convenient biochemical tumor marker after total or near-total resection of DTC and radioiodine therapy. Regular monitoring of Tg and thyroglobulin antibody (TgAb) in the long-term follow-up of patients is of extreme importance for disease surveillance. However, high serum levels of TgAb can be detected in up to 25% of patients with DTC, which will interfere with the accuracy of Tg assay. During which, the trends of TgAb can be served as a surrogate indicator to reflect the tumor status. A falling TgAb trend over time often indicates the remission or improvement of the disease. On the contrary, a sustained rising TgAb trend may be an early indicator of recurrence or metastases of DTC. Herein, the authors mainly reviewed the possible mechanism TgAb production and its clinical relevance in DTC.