〔Abstract〕 To investigate the inhibitory effect of Elesclomol (ES) + Cu2 + on the proliferation of human hepatoma cell lines PLC/PRF/5 and Huh-7 and its potential to induce Cuproptosis. Methods Human hepatoma cell lines PLC/PRF/5 and Huh-7 cells were Cultured in vitro. ES solution , Cu2 + solution and copper chelating a- gent ammonium tetrathiomolybdate VI (ATTM) solution was treated separately or in combination. The effect of ES + Cu2 + on the survival rate of human hepatoma cell lines PLC/PRF/5 and Huh-7 cells and the effect of ES + Cu2 + on the survival rate after pretreatment with copper chelating agent ATTM were evaluated using CCK-8 kit. The cell intervention at 100 mg/kg and 200 mg/kg effectively reversed these changes , lowering MDA and NOX4 levels( t = 3. 35 , 4. 30 , P < 0. 05 ; t = 5. 44 , 7. 44 , P < 0. 01) , while restoring SOD ( t200 mg/kg = 4. 04 , P < 0. 05) and GSH ( t = 4. 70 , P < 0. 05 ; t = 5. 50 , P < 0. 01) . Endoplasmic reticulum stress markers , including GRP94、GRP78、p- elF2α、CHOP ( t = 3. 31 , 6. 53 , 5. 18 , 3. 09 ; P < 0. 05 , 0. 01 , 0. 01 , 0. 05 ) , were significantly upregulated in the DEX group compared to the normal group. However, TGP treatment at 100 mg/kg and 200 mg/kg dose-dependent- ly suppressed the expression of GRP94、GRP78、p-elF2α、CHOP ( t = 3. 14 ,4. 95 , 3. 13 ,4. 25 , P < 0. 05 ; t = 4. 03 , 7. 48 ,4. 68 ,5. 10 ,P < 0. 01) expression levels were significantly reduced compared to the DEX group , and there was no significant change in the TGP (50 mg/kg) treatment group. Conclusion TGP exerts protective effects a- gainst DEX-induced liver injury , and its mechanism is likely mediated by suppressing hepatic oxidative stress and endoplasmic reticulum stress triggered by DEX in rats.