Introducion: To explore the intervention mechanism of Kaiyu Zhengyuan powder on epithelial mesenchymal transformation and apoptosis of papillary thyroid carcinoma.Materials and methods: Kaiyu Zhengyuan powder was used to intervene TCP1 cells and divided into blank group, inhibitor group, and traditional Chinese medicine group; The indexes were detected by Western blotting and flow cytometry.Results: Kaiyu Zhengyuan Powder can effectively reduce ER alpha, GPER protein expression level in estrogen receptor pathway,increase ER beta Protein expression level.It can effectively reduce the expression level of angiogenic factors VEGF and BFGF, and also down regulate GSK-3 alpha,GSK-3 beta Protein expression level. The expression level of Twist1,HIF-1 alpha,PFK,PKM2 protein that closely related to epithelial mesenchymal transformation were decreased.Reduce the expression level of PI3K, AKT1, P70S6K, PDK1,cyclin D1,Bcl2 and p21 proteins, promote apoptosis, increase the expression level of Bax protein in apoptotic proteins.Flow cytometry showed that Kaiyu Zhengyuan Powder promoted TCP1 cell apoptosis.Conclusion: Kaiyu Zhengyuan Powder can inhibit the epithelial mesenchymal transformation of papillary thyroid carcinoma to a certain extent, so as to prevent the metastasis of papillary thyroid carcinoma, and it has a good therapeutic efect on papillary thyroid carcinoma by interfering with PI3K/AKT signal pathway.