How to control the frequent occurrence of cyanobacteria, especially the outbreak of toxin-producing Microcystis aeruginosa, has been a subject of constant research. This investigation focused on the effect of Moina mongolica on restricting M. aeruginosa blooms under different variables (temperature, light intensity, and salinity) and its growth at the molecular level. The results of batch experiments showed that the range of M. mongolica feeding rates was from 4.02 ± 0.81 × 10sup.3~182.23 ± 5.37 × 10sup.3 cells/ind·h in the whole experiment, where the highest feeding rates of larva M. mongolica and adult M. mongolica were 133.21 ± 5.24 × 10sup.3 vs. 182.23 ± 5.37 × 10sup.3 cells/ind·h at 30 °C, 85.88 ± 0.44 × 10sup.3 vs. 143.15 ± 14.07 × 10sup.3 cells/ind·h at 3000 lx and 88.18 ± 0.32 × 10sup.3 vs. 84.49 ± 4.95 × 10sup.3 cells/ind·h at 0‰ salinity, respectively. The results of transcriptomics further demonstrated that the response of M. mongolica to M. aeruginosa toxicity was caused by the downregulation of relevant functional genes (cell components, cell processes, metabolic processes, and protein complexes) and related signaling pathways (apoptosis, phagosome, lysosome, ribosome, oxidative phosphorylation, amino and nucleoside sugar metabolism, and PPAR signaling pathways). The findings show that M. mongolica can be released to low-salinity lakes and coastal areas (the subtropic and temperate zones) to prevent and inhibit M. aeruginosa blooms in the early summer phase. Additionally, the results achieved by the investigation will provide the relevant technology for inhibiting cyanobacteria blooms because M. mongolica even resists the produced toxin by M. aeruginosa.