We have shown that several natural products can regulate pancreatic CSC characteristics and inhibit tumour growth by suppressing the Shh‐Gli pathway.8, 9, 10, 11, 32, 36, 37, 38, 39 In the present study, we demonstrate that α‐Mangostin modulates several critical components of the Shh pathway to inhibit the proliferation of pancreatic cancer cell lines and CSCs. This evidence concerns the gene SHH and pancreatic neoplasm.