Abstract: Objective Based on the inhibition of Keap1(Kelch-like ECH-associated protein 1)gene, we studied the effects of arsenic exposure on the apoptosis and antioxidant capacity of human immortalized keratinocyte (HaCaT) cells. Methods The cells were cultured for 72 h and was divided into 5 groups including blank control, negative control (Keap1 gene inhibition of untouched arsenic) and Keap1 gene inhibition+low-dose arsenic group (2.9 μmol/L), Keap1 gene inhibition +medium-dose arsenic group (5.8 μmol/L) and Keap1 gene inhibition +high-dose arsenic group (29.0 μmol/L); The apoptosis rate was detected by flow cytometry. The expression of Nrf2 and Keap1 mRNA was detected by Real-Time Quantitative PCR. The expressions of GSH, HO-1, COX-2, SAM and HCY were detected by ELISA. Results The expression of Nrf2 and Keap1 mRNA was not equal in each groups (all P<0.05). Compared with the negative control group, the expression of SAM and HCY protein in low-dose arsenic group was significantly increased (all P<0.05); The protein expression of COX-2 was increased in medium-dose and high-dose arsenic groups (all P<0.05); GSH protein expression was increased in high arsenic group (F=7.24,P=0.001). Conclusions In the case of Keap1 gene inhibition, the arsenic exposure increased the antioxidant enzyme activity, increased the level of antioxidation and decreased the apoptosis rate. With the increasing of arsenic dose, the expression of Nrf2 was down-regulated and the antioxidant level was imbalanced and death increased.