A suspension of Microcystis aeruginosa (30 μg L−1chlorophyll a) was circulated in a hydrodynamic cavitation device and ozone was introduced at the suction side of the pump. The removal of algae over 10 min using hydrodynamic cavitation alone and ozone alone is less than 15% and 35%, respectively. The destruction of algae rises significantly from 24% in the absence of the orifice to 91% with the optimized orifice on 5 min of processing using hydrodynamic cavitation along with ozone (HC/O3) and the utilization of ozone increases from 32% to 61%. Interestingly, the suction process is more effective than the extrusion method (positive pressure) and the optimal bulk temperature for algal elimination was found to be 20 °C. Increasing the input concentration of ozone is favorable for the removal of algae but leads to a greater loss of ozone and a decrease in the utilization of ozone. Under the optimal conditions, the algal cells and chlorophyll a are completely destroyed in 10 min by use of the hybrid method.