Inspired by advances in stem cell and reprogramming field, here it is reported that a small molecule cocktail (SMC) consisted of: SB431542 (TGFβ inhibitor), CHIR99021 (GSK3β inhibitor), BIX01294 (H3K9 methyltransferase/G9a inhibitor), and all‐trans retinoic acid (ATRA), can induce differentiation of liver cancer cells including cell lines, primary cancer cells, cancer stem cells, and drug resistant cells. This evidence concerns the gene EHMT2 and liver cancer.