Abstract: The culture of Acrossocheilus wenchowensis is often challenged by hypoxia. To investigate the effects of hypoxia on the physiological and biochemical responses of A. wenchowensis, we exposed the fish to chronic hypoxia Dissolved oxygen: (2.50±0.30) mg·L⁻¹ for 7 d, followed by 7 d of reoxygenation under normoxic conditions. The activities of superoxide dismutase (SOD) and catalase (CAT) in liver tissue were determined, the histological microstructure of the liver was observed, and the expression levels of related genes were analyzed. The results show that, compared with the control group (Normoxia), hypoxia stress increased hepatic SOD activity but decreased CAT activity. Hepatocytes showed extensive vacuolization and disordered arrangement. After reoxygenation, SOD activity returned to normal levels, while CAT activity remained relatively low. Vacuolization was alleviated, but cellular disorganization persisted. Hypoxia up-regulated the expression of Hif-1α, p53, and Bax, and down-regulated Bcl-2. These gene expressions gradually returned to baseline levels after reoxygenation. The findings indicate that chronic hypoxia activates the Hif-1α and p53 genes, up-regulates Bax, and promotes hepatocyte apoptosis, leading to liver injury. Reoxygenation restores Hif-1α and p53 expression to normal, inhibits apoptosis, and facilitates tissue recovery. This study provides morphological evidence and theoretical support for understanding the physiological response mechanisms of fish under hypoxic conditions.