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The large yellow croaker (Larimichthys crocea) is one of the most important marine economic fish in the southeast coast of China. However, hypoxia stress become a major obstacle to the benign development of L. crocea industry. To understand the energy metabolism mechanism adapted to hypoxia, we analyzed the transcriptome and physiology of L. crocea liver in response to hypoxia stress for different durations. We obtained 243,756,080 clean reads, of which 83.38% were successfully mapped to the reference genome of L. crocea. The heat map analysis showed that genes encoding enzymes involved in glycolysis/gluconeogenesis were significantly upregulated at various time points. Moreover, genes encoding enzymes related to the citrate cycle, oxidative phosphorylation, and amino acid metabolism were significantly downregulated at 6 and 24 h, but upregulated at 48 and 96 h. The change of liver in physiology processes, including respiratory metabolism, and activities of the carbohydrate metabolism enzymes showed a similar trend. The results revealed that the respiratory metabolism of L. crocea was mainly anaerobic within 24 h of hypoxia stress, and aerobic metabolism was dominant after 24 h. Carbohydrate metabolism plays a crucial role in energy supply and amino acid metabolism is an important supporting character to cope with acute hypoxia stress. There was no significant change in lipid utilization under short-term acute stress. This study increases our understanding of the energy metabolism mechanism of the hypoxia response in fish and provides a useful resource for L. crocea genetics and breeding. • The transcriptome of L. crocea liver was analyzed under hypoxia stress. • The adjustment of energy metabolism might be an effective strategy through which L. crocea responds to hypoxia stress. • Anaerobic metabolism and aerobic metabolism play an important role in the L. crocea 's response to hypoxia stress. • Glycometabolism plays a crucial role in hypoxia adaptation and amino acid metabolism is an important supporting character. [ABSTRACT FROM AUTHOR]