Abstract: During the last few decades, the incidence of thyroid cancers has been escalating globally, with differentiated thyroid cancer(DTC) accounting for 90% of the cases. A portion of DTC dedifferentiates and becomes radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC), naturally or during cancer management. Currently, no consensus exists regarding the definition of RAIR-DTC, which to a certain extent influences its diagnosis and treatment. RAIR-DTC has always been a problem because its management lacks efficiency. As the understanding on the molecular pathophysiology of thyroid cancer continues to improve, targeted agents develop quickly, particularly in the treatment of RAIR-DTC, which will open up new directions for the management of thyroid cancer.