Abstract: OBJECTIVE To explore the antioxidant effect and mechanism of 7-hydroxyethyl chrysin in PC12 cells. METHODS Cell viability was detected by CCK-8, and the best concentration of 7-hydroxyethyl chrysin was selected for subsequent experiments. Then PC12 cells were divided into 4 groups:control group, hypoxia group, chrysin group and 7-hydroxyethyl chrysin group. LDH in cell culture medium was evaluated by the microplate method. ROS level was evaluated by DCFH-DA. The levels of MDA, SOD and CAT in the cells were measured by the test kit. Western blotting was used to evaluate Nrf2 and its downstream protein expression. RESULTS The cell viability was reduced after hypoxia, it can be improved after pretreatment with 7-hydroxyethyl chrysin. LDH in the cell culture medium, ROS and MDA levels in the cells of chrysin group and 7-hydroxyethyl chrysin group were also significantly reduced compared with the hypoxia group, the activity of SOD and CAT was also significantly increased when compared with the hypoxia group, it was also found that the effect of 7-hydroxyethyl chrysin was significantly higher than chrysin in all aspects. Meanwhile, hypoxia could increase the protein expression of Nrf2, Keap1, HO-1, NQO1, and 7-hydroxyethyl chrysin could further improve their protein expression. CONCLUSION The protective effect of 7-hydroxyethyl chrysin is better than that of chrysin. It can reduce the damage of PC12 cells caused by hypoxia by activating the Nrf2/ARE pathway.