Abstract: Provided are a small molecule compound combination for reprogramming digestive tract derived epithelial cells to endodermal stem/progenitor cells, a reprogramming method and an application. Human gastric epithelial cells (hGECs) are used as initiating cells, human gastric subepithelial myofibroblasts (aGSEMFs) are used as a trophoblast, a compound combination having all or a plurality of FBP, Bay K 8644, Bix01294, SB431542 or A813-01, VPA, RG108, PD0325901 and PS48 including SB or A83 is used to reprogram digestive tract derived epithelial cells to endodermal stem/progenitor cells, and the endodermal stem/progenitor cells can be used for inducing differentiation towards liver cells, pancreatic beta cells and intestinal cells.