Bloom forming algae and hypoxia are considered to be two main co-occurred stressors associated with eutrophication. The aim of this study was to evaluate the interactive effects of harmful algae Microcystis aeruginosa and hypoxia on an ecologically important mussel species inhabiting lakes and reservoirs, the triangle sail mussel Hyriopsis cumingii, which is generally considered as a bio-management tool for eutrophication. A set of antioxidant enzymes involved in immune defence mechanisms and detoxification processes, i.e. glutathione-S-transferases (GST), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), lysozyme (LZM) in mussel haemolymph were analyzed during 14days exposure along with 7days depuration duration period. GST, GSH, SOD, GPX and LZM were elevated by toxic M. aeruginosa exposure, while CAT activities were inhibited by such exposure. Hypoxia influenced the immune mechanisms through the activation of GSH and GPX, and the inhibition of SOD, CAT, and LZM activities. Meanwhile, some interactive effects of M. aeruginosa, hypoxia and time were observed. Independently of the presence or absence of hypoxia, toxic algal exposure generally increased the five tested enzyme activities of haemolymph, except CAT. Although half of microcystin could be eliminated after 7days depuration, toxic M. aeruginosa or hypoxia exposure history showed some latent effects on most parameters. These results revealed that toxic algae play an important role on haemolymph parameters alterations and its toxic effects could be affected by hypoxia. Although the microcystin depuration rate of H. cumingii is quick, toxic M. aeruginosa and/or hypoxia exposure history influenced its immunological mechanism recovery.