Abstract： Objective To explore the effect of knocking down astrocyte elevated gene-1(AEG-1)on diethylnitrosamine(DEN)-induced primary hepatocellular carcinoma(PHC).Methods A total of 60 rats were randomly divided into 4 groups:Control group,DEN group,AEG-1 NC KO DEN group and AEG-1 KO DEN group,15 rats in each group.Rats were given in-tragastric administration of DEN to construct PHC models in each group except in the Control group,while rats in the Control group were given the same volume of normal saline.The rats in AEG-1 KO DEN group and AEG-1 NC KO DEN group were given intraperitoneal injection of HCCLM6 with stably transfected AEG-1 shRNA or shRNA-NC lentivirus expression vector,respectively.The liver cell damage,apoptosis,levels of superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione peroxidase(GSH),liver function,levels of serum IL-6 and TNF-α,expressions of caspase-3(Cas-3),caspase-9(Cas-9)and P65 in liver tissues were compared among each group.Results The expression level of AEG-1 in the DEN group was significantly higher than that in the Control group(P<0.05).The mortality of rats and incidence of ascites in the AEG-1 KO DEN group were lower than those in the DEN group(P<0.05),and the levels of serum AST,ALT,IL-6 and TNF-α were lower than those in the DEN group(P<0.05),SOD activity was higher than that in the DEN group(P<0.05),levels of GSH and MDA were lower than those in the DEN group(P<0.05),and expressions levels of cleaved cas9/cas9,cleaved cas3/cas3 and p-P65/P65 were lower than those in the DEN group(P<0.05).Conclusion Knocking out AEG-1 can reduce the levels of oxidative stress and inflammatory factors induced by DEN,relieve liver tis-sue damage and improve liver function in rats.