Papillary thyroid carcinoma (PTC) is the most commonly diagnosed endocrine cancer, and those with BRAFV600E mutation have high recurrence rate and less favorable clinical behavior. Genistein having anti-carcinoma effects in various types of carcinomas as an estrogen analog, but the mechanism of Genistein in the progression of PTC remains unknown. Genistein significantly inhibits the proliferation and the invasion (P < 0.01), and the apoptosis (P < 0.001) of all tumor cell lines, which was probably due to the inducing of the arrest in G2/M phase of the cell cycle (P < 0.001). The anti-proliferation and apoptosis inducing effects are more obvious in BCPAP, IHH4 cell lines harboring BRAFV600E mutation. Genistein significantly decreased the invasion of PTC cell lines and partially reverses epithelial mesenchymal transition in PTC cell lines. Functional study indicated that small interfering RNA (siRNA) knockdown of β-catenin significantly reverses the effect of genistein on EMT at protein levels. In conclusion, for the first time, our study suggested that genistein has anticarcinoma effect for PTC patients in the range of 2.5 and 80 μg/ml in thyroid carcinoma cells, which was probably through cytoplasmic translocation of β-catenin. Further study will be needed to determine whether genistein could be used in clinical trial of high-risk PTC.