The results of this study showed that ALOF extract, along with SIL, can have synergistic effects through improving antioxidant parameters, suppressing inflammatory pathways, and regulating the apoptotic/survival pathways of PI3K/Akt/mTOR and Bax/Bcl‐2/Cas‐3/p53 for preserving the physiological function of hepatocytes and the structure of liver lobules against DEN‐induced hepatocellular carcinoma. Here, TP53 is linked to hepatocellular carcinoma.