To study the physiological regulatory mechanisms of Changfeng silver carp(Hypophthalmichthys molitrix, CF) on continuous hypoxia stress, the blood indicators, tissues antioxidant enzymes activities and genes expression levels were analysed at different time(0, 3, 6, 12, 24, 36, 48, 60, 72, 84 h) after hypoxia treatment with a dissolved oxygen of (2.0±0.5) mg/L. The results showed that continuous hypoxia stress caused a significant increase of hemoglobin content and white blood cell count in blood, and a significant increase of the total antioxidant capacity in the serum. In addition, under continuous hypoxia stress, the GSH-Px activity in liver of CF decreased significantly except for 36 and 48 h, and the GSH-Px activity in brain was significantly lower than that in control group within 24 to 60 h. The CAT activity in the liver of CF increased significantly from 36 h, and the CAT activity in the brain increased from 6 h, and decreased significantly at 60 h and later. The SOD activity in the liver of CF rapidly decreased to the lowest value within 3 h after hypoxia stress, and then showed a slow rising trend, but it was still significantly lower than that of the control, while the SOD activity in the brain began to rise from 3 h, except for 72 h, and was equal to or significantly higher than that of the control group. The expression levels of HIF-1α and phd3 in the brain and liver fluctuated under hypoxia stress, while they were higher than those of the control at most of time points. These results indicated that CF increased delivery of oxygen by improving hemoglobin content, and this physiological response might be regulated by the expression of HIF-1α and phds. Furthermore, the antioxidant enzyme systems of brain and liver of CF were activated to resist tissue damage induced by continuous hypoxia stress.