Abstract: Thyroid cancer is the most common endocrine malignancy, and ninety percent is differentiated thyroid cancer. Surgery, radioactive iodine treatment, TSH suppressive therapy is one of the trilogies of differentiated thyroid cancer treatment. Although the diagnosis and treatment of differentiated thyroid cancer is very mature, there are some patients cannot benefit from the radioactive iodine treatment naming RAI-refractory DTC. For these patients showing dedifferentiated and a lower level of iodine uptake now use targeted drugs achieving curative effect. The studies of molecular pathology of thyroid provide a theoretical basis for the diagnosis and treatment of thyroid cancer. This review comprehensively discussing the progress of molecular targeted therapy about refractory thyroid cancer.