Pancreatic cancer is a lethal disease, and new treatments need to be explored. Huaier extract is a traditional Chinese medicine that has been found to exert antitumor properties in some cancers. However, the role of Huaier extract in pancreatic cancer has not been examined. In this study, we found that the proliferation, migration, invasion and EMT (epithelial-mesenchymal transition) of pancreatic cancer cells were suppressed by treatment with Huaier extract and that apoptosis increased. We also observed that expression of β-catenin was inhibited by Huaier extract. Furthermore, an animal study showed that Huaier extract slowed tumor growth in pancreatic cancer. Our results reveal that Huaier extract suppresses pancreatic cancer by inhibiting Wnt/β-catenin pathway both in vitro and in vivo.