Harmful　algal　bloom　stimulated　by　eutrophication　has　gained　increasing　attention　worldwide.　This　phenomenon　deteriorates　water　quality　and　destroys　the　local　ecological　equilibrium,　and　thus　must　be　addressed.　Ultrasound　can　effectively　inhibit　the　growth　of　bloom　algae,　but　its　effect　on　the　organic　matter　of　Microcystis　aeruginosa　cells　remains　unknown.　Moreover,　the　mechanism　of　ultrasonic　irradiation　is　unclear.　This　study　investigated　algal　biomass,　zeta　potential,　organic　matter,　and　protein　after　treatment　with　different　ultrasonic　frequencies　and　power　densities　to　optimize　ultrasonic　parameters　and　reveal　the　mechanism　of　the　effect　of　ultrasonic　irradiation　on　algae.　Results　showed　that　low-frequency　ultrasonic　irradiation　effectively　inhibited　blue　algae　growth.　The　zeta　potential,　ribulose-1,5-bisphosphate　carboxylase/oxygenase　(RuBisCO)　protein　gray　value,　and　phycobiliprotein　level　decreased,　whereas　the　fluorescence　peak　of　fulvic　acid　and　dead　cells　increased.　The　damage　to　the　RuBisCO　protein　in　algae　treated　by　ultrasonic　frequency　of　40　kHz　was　more　severe　than　that　in　algae　treated　by　the　frequency　of　20　and　100　kHz　under　the　power　density　of　0.0628　W/mL.　The　high　ultrasonic　density　caused　severe　damage　to　the　RuBisCO　protein　and　photosynthesis.　Under　a　specific　ultrasonic　frequency,　higher　power　density　leads　to　more　obvious　inhibition　on　algae　cells.　Thus,　the　growth　of　M.　aeruginosa　can　be　controlled　under　the　optimal　ultrasonic　frequency　and　power　density　of　40　kHz　and　0.0628　W/mL,　respectively.　©　2018　Desalination　Publications.