The　clinical　prospect　of　sonodynamic　therapy　(SDT)　has　not　been　fully　realized　due　to　the　scarcity　of　efficient　sonosensitizers.　Herein,　we　designed　phthalocyanine–artesunate　conjugates　(e.g.　ZnPcT4A),　which　could　generate　up　to　ca.　10-fold　more　reactive　oxygen　species　(ROS)　than　the　known　sonosensitizer　protoporphyrin　IX.　Meanwhile,　an　interesting　and　significant　finding　of　aggregation-enhanced　sonodynamic　activity　(AESA)　was　observed　for　the　first　time.　ZnPcT4A　showed　about　60-fold　higher　sonodynamic　ROS　generation　in　the　aggregated　form　than　in　the　disaggregated　form　in　aqueous　solutions.　That　could　be　attributed　to　the　boosted　ultrasonic　cavitation　of　nanostructures.　The　level　of　the　AESA　effect　depended　on　the　aggregation　ability　of　sonosensitizer　molecules　and　the　particle　size　of　their　aggregates.　Moreover,　biological　studies　demonstrated　that　ZnPcT4A　had　high　anticancer　activities　and　biosafety.　This　study　thus　opens　up　a　new　avenue　the　development　of　efficient　organic　sonosensitizers.　©　2021　Wiley-VCH　GmbH.