Objective:To investigate the effect of human Cu/Zn superoxide dismutase (hSOD1) gene with G93A mutation on Nrf2/ARE signaling pathway in NSC‐34 cell ,the transgenic cell model of amyotrophic lateral sclerosis (ALS) .Methods :The established plasmids ,hSOD1‐pcDNA3 .1(‐) ,hSOD1‐G93A‐pcDNA3 .1(‐) ,and pcDNA3 .1(‐) were transfected into NSC‐34 cells ,the transgenic cell model of amyotrophic lateral sclerosis .The models were divided into four groups according to different transfected plasmids .They were normal group ,empty group ,wild group and mutation group .The oxidative‐stress injury was evaluated by detecting the content of intracellular malondialdehyde (MDA) ,a lipid peroxidation product .The permeability of mitochondrial membrane was detected .Western blotting was used to determine the intracellular protein expression level of Nrf 2 and antioxidase ,so as to reveal the activation level of the Nrf2/‐ARE signaling pathway in each group .Results:The level of oxidative stress and the mitochondrial permeability increased in the NSC‐34 cells transfected with human hSOD1‐G93A‐pcDNA3 .1(‐) gene(mutation group ,P<0 .05) ,which implied impairment of mitochondrias .The protein expression level of Nrf2 ,significantly decreased in NSC‐34 cells transfected with hSOD1‐G93A gene(P< 0 .05) .So were heme oxygenase‐1 (HO‐1) and NAD(P)H :quinone oxidoreductase 1 (NQO1) ,downstream effector molecules of Nrf2‐ARE signaling pathway . The expression of Nrf 2 in cytoplasm significantly decreased in mutation group , while Nrf2 expression in cell nucleus significantly increased (P<0 .05) in mutation group and wild group ,especially in mutation group (P<0 .05) .Conclusions :The G93A mutation of hSOD1 gene impairs Nrf2/ARE signaling pathway in ALS cell models ,reduces the antioxidant ability of cells ,and increase the impairment of mitochondrias .