Leucine-rich-alpha-2-glycoprotein 1 (LRG-1) has been reported to be associated with multiple malignancies. However, its participation in thyroid carcinoma progression remains unclear. In the present study, the biological function and underlying molecular mechanisms of LRG-1 in thyroid carcinoma were investigated. It was found that LRG-1 was overexpressed in thyroid carcinoma tissues, and high LRG-1 expression predicted poor patient survival and late tumor stage. As shown in the mouse xenograft study, knockdown of LRG-1 significantly attenuated thyroid cancer growth in vivo . Based on wound healing, Transwell, proliferation and apoptosis assays, it was found that the knockdown of LRG-1, using shLRG-1, inhibited cell migration and invasion, but did not affect proliferation and apoptosis in thyroid cancer cells . Furthermore, LRG-1 also induced epithelial-mesenchymal transition (EMT) in thyroid carcinoma cells. Western blot analysis revealed that this tumor-promoting bioactivity of LRG-1 was attributed to its selective activation of MAPK/p38 signaling. All of these findings indicate that LRG-1 plays a deleterious role in the progression of thyroid carcinoma. LRG-1 may serve as a promising biomarker for predicting prognosis in thyroid carcinoma patients, and LRG-1-based therapy may be developed into a novel strategy for the treatment of thyroid carcinoma.