In conclusion, (a) baicalin inhibits human HCC cells by inducing apoptosis; (b) baicalin induces cell apoptosis by activating ATF6 signaling pathway in endoplasmic reticulum (ER) stress; (c) S2P, rather than S1P is the molecular target for baicalin in inducing ER stress‐mediated HCC cell apoptosis. The gene discussed is MBTPS2; the disease is hepatocellular carcinoma.