In order to clarify the toxic effects of hypoxia and toxic Microcystis aeruginosa on freshwater pearl mussel (Hygriopsis cumingii) and histopathology, scanning electron microscopy was used to investigate the histopathological changes in the gill, stomach, intestine and crystal rod of the freshwater pearl mussel. The results showed that a large number of gill shedding and columnar cell necrosis were observed from the seventh day in the combined experimental group with hypoxia and toxic algae, as well as cilia loss from gastrointestinal cavity surface and epithelial cell necrosis rupture, and the crystal rod completely disappeared from the fifth day; from the seventh day, in hypoxia group and toxic algae group, a small amount of gill and digestive tract lesions were observed, and in hypoxia group, crystal rod completely disappeared from the seventh day, while in toxic algae group, the crystal rod persists throughout the experiment. After the stress was removed, in the three exposed groups, the crystal rods did not return to the normal levels as in the control group. Therefore, hypoxia and toxic Microcystis aeruginosa caused unrecoverable damages in gill and digestive system of H. cumingii, and the combined stress group was most severely affected, and hypoxia caused more severe effects than the toxic Microcystis aeruginosa. This study provides a histopathological reference for the physiological adaptation mechanisms in H. cumingii exposed to hypoxia and toxic algae, and a theoretical basis for the feasibility of H. cumingii as a bioremediation tool species for improving eutrophic waters.