Plants or herb extracts have emerged as a novel approach to controling various diseases, including cancers. Among them, Pulsatilla koreana extract (PKE) has been widely used as an anti-inflammatory agent and for treating dysentery in traditional Korean and Chinese medicine. However, the effect of PKE as a cancer drug candidate has been less reported. Thus, we investigated the effect of PKE on cell growth and its mechanism in anaplastic thyroid cancer (ATC) cells. In this study, PKE suppressed the growth of ATC cells in a dose-dependent manner. Additionally, PKE induced apoptosis by increasing expression of cleaved PARP and caspase-3 in ATC cells. The apoptotic effect of PKE was confirmed by diamidino-2-phenylindole (DAPI) and terminal deoxynucleotidyltransferase-mediated nick end labeling (TUNEL) assay, showing apoptotic body and DNA fragmentation. In addition, PKE decreased the expression of hypoxia-inducible factor 1α (HIF‑1α) and vascular endothelial growth factor (VEGF) as well as inhibiting tube formation and migration of human umbilical vein endothelial cells (HUVECs). Furthermore, in vivo studies showed that PKE significantly inhibited tumor growth and weight in a mouse xenograft model. Taken together, the present study demonstrated that PKE induced apoptosis, as well as inhibiting cell growth and angiogenesis in ATC cells. We suggest that PKE is a potent anticancer drug candidate for the treatment of thyroid cancer.