Plenty of freshwater species, especially macroinvertebrates that are essential to the provision of numerous ecosystem functions, encountered higher mortality due to acute hypoxia. However, within the family Chironomidae, a wide range of tolerance to hypoxia/anoxia is displayed and Propsilocerus akamusi depends on this great endurance to become a dominant species in eutrophic lakes. To further understand how P. akamusi responds to acute hypoxic stress, we used multi-omics analysis in combination with histomorphological characteristics and physiological indicators. To evaluate enzyme activity, the transcriptome and metabolome, and histomorphological characteristics, we set up two groups: a control group (DO 8.4mg/L) and a hypoxic group (DO 0.39mg/L). With blue-black chromatin, cell tightness, cell membrane invagination, and the production of apoptotic vesicles, tissue cells displayed typical apoptotic features. While lactate dehydrogenase (LDH), (Alcohol dehydrogenase) ADH, catalase (CAT), and Na+/K+ -ATPase (NKA) activities were dramatically enhanced under hypoxic stress, glycogen content, and superoxide dismutase (SOD) activities were significantly reduced compared to the control group. The above results were further supported by the joint analysis of the transcriptome and metabolome, which further revealed that in addition to carbohydrates, including glycogen, the energy metabolism of the fatty acid, trehalose, and glyoxylate cycles is also included. Furthermore, we also revealed the ethanol tested in hypoxic stress should derive from symbiodinium of P akamusi. Understanding the processes which enable P. akamusi to survive lengthy periods of hypoxia in eutrophic lakes might help to design sensitive biomonitoring procedures, and this species has the potential to be used as an effective eutrophication indicator.