The aim of the present study was to evaluate the effects of β-glucan on acute hypoxia-induced oxidative stress by determining lipid peroxidation, activities and mRNA levels of antioxidant enzymes (Cu/Zn-SOD, CAT, GPx and GR), and gene expressions of the Keap1-Nrf 2 signaling molecules in the liver of large yellow croaker Larimichthys crocea. Fish were injected with β-glucan at a dose of 0 or 5 mg/kg body weight on 6, 4 and 2 days before being exposed to 1.5 and 7.0 DO mg/L for 24 h. The results showed that normoxia with β-glucan had no effect on lipid peroxidation compared with the normoxic control, and hypoxic stress with β-glucan remarkably reduced lipid peroxidation during the whole experiment compared with hypoxic stress, indicating that β-glucan could ameliorate hypoxia-induced lipid peroxidation. Obtained results also showed a coordinated transcriptional regulation of antioxidant genes, suggesting that Nrf 2 was required for regulating these genes. Furthermore, a negative relationship between the mRNA levels of Nrf 2 and Keap1 indicated that Keap1 plays an important role in switching off the Nrf 2 response. In conculsion, β-glucan could alleviate acute hypoxia-induced oxidative stress in large yellow croaker, emphasizing a central role of transcription factor Nrf 2 in the process.