The effect of 131I therapy for primary and metastatic lesions of thyroid carcinoma depends on the ability of iodine uptake.The loss or down-regulation of iodine-metabolizing genes represents dedifferentiation of DTC,which results in the disability to take up and accumulate 131I and eventually leads to radioiodine-refractory DTC (RR-DTC).The management of RR-DTC is extremely difficult and the prognosis is poor.It is important for the treatment and prognosis of RR-DTC to investigate the mechanism of redifferentiation.The up-regulation of thyroid iodine-metabolizing genes expression,inhibition of the changes in epigenetic modifications and intervention of the abnormal activation of signaling pathways are reviewed in this article.