Both in vivo and in vitro data provided convincing evidences that silencing or the antagonist of GPR65 inhibited, while overexpression or the application of the endogenous and exogenous agonist of this receptor enhanced the expression and release of TNF-α, IL-6 and TGF-β, all of which promoted the activation of HSCs and the damage of HCs, and subsequently aggravate BDL- and CCl4-induced hepatic inflammation, injury and fibrosis. The gene discussed is TNF; the disease is inflammation.