By co-culturing tumor cells and adjacent stromal cells, studies have revealed that the Hh ligand produced by tumor cells can be taken up by surrounding stromal cells which can secrete some paracrine signals (such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF) and other factors) promoting tumor growth to stimulate the Hh pathway, that is, the paracrine model [33, 67, 68], occurred in ovarian cancer, hepatocellular carcinoma (HCC), prostate cancer, breast cancer and other cancers [3, 69–71]. Here, IGF1 is linked to hepatocellular carcinoma.