Our results have for the first time indicated that CYP1A2 may mediate the inhibitory effect of E2 by facilitating E2 metabolism to generate the cytotoxic 2-ME in HCC and that the reduction of CYP1A2 expression observed in HCC may thus damage the metabolic homeostasis of liver to fight against cancer, which may lead to the development and progression of HCC. Here, CYP1A2 is linked to hepatocellular carcinoma.