Abstract: Heme oxygenase 1 (Ho1) is the rate-limiting enzyme in the degradation of heme into biliverdin, carbon monoxide and free divalent iron. Abnormal expression of ho1 gene is associated with the development and progression of various human diseases, while functions of zebrafish Ho1 under hypoxia stress remain largely unknown. This study explored the protection role of zebrafish Ho1 during hypoxia exposure. The results showed that hypoxia significantly induced zebrafish ho1 mRNA in ZF4 cells, embryos, brain, gill, and liver but significantly decreased it in heart and kidney after 24h hypoxic exposure. Ho1 inhibition by ZnPPIX decreased ZF4 cell viability under hypoxia stress, enhanced Ho1 activity protected ZF4 cell from hypoxia stress-induced cell death. These results showed that Ho1 may protect zebrafish from hypoxia-induced cell apoptosis.