In this study, we identified the functions of GRHL2 in NAFLD and further found that SIRT1 down‐regulation induced by GRHL2‐dependent miR‐200 or MAPK signalling pathway activated by GRHL2 exacerbated liver fibrosis and intestinal mucosal barrier dysfunction in NAFLD. The gene discussed is SIRT1; the disease is Hepatic fibrosis.