In the present study, the hypoxia tolerance and alternation of hematological, physiological, and biochemical parameters, gill histology, and hepatic antioxidant capacity subjected to hypoxia stress were investigated in black scraper Thamnaconus modestus. The closed static water method was used to analyze the dissolved oxygen (DO) levels at critical oxygen tension (P_crit) and loss of equilibrium (LOE) in black scraper. Subsequently, changes in hematological, physiological, and biochemical parameters, gill histology, and hepatic antioxidant enzyme activity were detected at P_crit, LOE, reoxygenation 3 hours (R3) and 6 hours (R6). The results showed that the DO concentrations of the black scraper [(101.23±14.28) g] at P_crit and LOE were (4.0±0.2) mg/L and (2.2±0.2) mg/L, respectively. Hypoxia significantly increased glucose and cortisol levels. White and red blood cell numbers also increased with the highest value observed at LOE (P＜0.05). The hemoglobin concentration and hematocrit showed an upward trend at LOE, but the difference was not significant (P＞0.05). Meanwhile, hypoxia significantly increased the length, width, basal epithelial thickness, and perimeter of the secondary lamellae, and decreased interlamellar distance and the proportion of available gas exchange (P＜0.05). Hypoxia stress also induced branchial clubbing, fusion, and matrix hyperplasia of the secondary lamellae. Hepatic superoxide dismutase, catalase, glutathione peroxidase activity, and malondialdehyde levels significantly increased under hypoxia (P＜0.05), peaking at LOE. Reoxygenation treatment for 6 hours alleviated the stress mentioned above effects. These results indicated that hypoxia stress lead to significantly alterations in the black scraper's hematological, physiological and biochemical profiles, gill morphology, and hepatic antioxidant capacity, which are substantially alleviated after 6 hours re-oxygenation. These findings provide valuable insights into the physiological mechanisms underlying hypoxia tolerance and support the development of efficient and healthy breeding practices for black scraper.