Abstract: 【Objective】 This study aimed to elucidate the hypoxia adaptation strategies and molecular mechanisms of the flow-resistant F₁ generation （FDTL） of Larimichthys crocea， thereby providing theoretical support for breeding hypoxia-tolerant and flow-resistant strains， as well as scientific basis for optimizing environmental regulation in deep sea aquaculture to ensure high-quality industrial development. 【Method】 FDTL Larimichthys crocea cultured for 26 months and non-selected Larimichthys crocea （FDCL） were subjected to hypoxia stress （dissolved oxygen 2.0 ±0.1 mg/L） for 24 h. Liver， kidney， and gill tissues were collected at 5 time points （0， 6， 12， 18， and 24 h of hypoxia stress） to analyze expression of hypoxia response genes in liver and activities of antioxidant and metabolic enzymes in tissues， with gill sections were made. 【Result】 After 24 h of hypoxia stress， the relative expression of 8 hypoxia stress-related genes （ddit4， gadd45b， pfkfb3， egln3， angpt2， serpine1， atf3， hspb7） in the liver of FDTL Larimichthys crocea was extremely significantly lower than that in FDCL Larimichthys crocea （P<0.01， the same below）， whereas the expression of cpt1b and gclm was significantly （P<0.05， the same below） or extremely significantly higher than that in FDCL Larimichthys crocea. During hypoxia stress， the different temporal dynamic responses and differences between groups in indicators related to oxidative stress and metabolism in tissues were found between FDCL and FDTL Larimichthys crocea. The malondialdehyde （MDA） content in liver and gill tissues of FDTL Larimichthys crocea fluctuated relatively mildly， and the MDA content in kidney was significantly or extremely significantly lower than that in FDCL Larimichthys crocea. Activities of core antioxidant enzymes such as glutathione peroxidase （GSH-Px） and catalaes （CAT） were generally higher than those in FDCL Larimichthys crocea at most time points， with coordinated optimization among enzyme activities. The peak pyruvate kinase （PK） activity in liver and kidney tissues occurred at the mid-hypoxia stage （12 h）， closely mat-ching the peak energy demand during the mid-stress stage. At 6 h of hypoxia stress， the gill tissue of FDTL Larimichthys crocea remained structurally intact； mild parenchymal cell necrosis and capillary congestion appeared only after 18 h of stress， and no inflammatory cell infiltration was observed at any time point， indicating significantly greater tolerance to hypoxic environment compared with FDCL Larimichthys crocea. 【Conclusion】 FDTL Larimichthys crocea establishes an efficient molecular regulatory network by down-regulating expression of stress-responsive genes such as ddit4 and gadd45b while up-regulating expression of cpt1b and gclm genes. The activities of metabolic and antioxidant enzymes in tissues exhibit temporal adaptation characteristics， and the gill tissue shows stronger structural stability and anti-damage capacity. The advantage of hypoxia tolerance of FDTL Larimichthys crocea comes from a multi-dimensional synergy of “molecular regulation-physiological adaptation-tissue stability”， with the core being a lower threshold for hypoxia tolerance， efficient metabolic reprogramming， and enhanced resistance to gill tissue damage.