Abstract. In differentiated thyroid cancer (DTC), the association between thyroid-stimulating hormone receptor (TSHR) and metastasis, and the underlying molecular mechanisms remain unclear. The role of TSHR in the epithelial-mesenchymal transition (EMT) has not yet been reported, to the best of our knowledge. In the present study, the role of TSHR in the distant metastasis of DTC was investigated. TSHR was significantly downregulated in well-differentiated thyroid cancer cells and tissues, and a lack of TSHR promoted thyroid cancer cell invasion and metastasis by inhibiting the EMT of thyroid cancer cells. In addition, the prognostic value of TSHR in thyroid cancer was analyzed. Immunohistochemical analysis of 172 DTC tissues revealed that a lack of expression of TSHR was associated with distant metastasis and a poor survival rate. Multivariate analyses demonstrated that TSHR expression was a significant prognostic factor for distant metastasis and survival time. The results from the present study demonstrated that TSHR inhibits metastasis through regulating EMT in vitro, and that a lack of expression of TSHR is a significant independent factor affecting distant metastasis and poor prognosis in DTC.