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Objectives: Sonodynamic therapy (SDT) is a promising non-invasive adjuvant approach for treating accessible tumors, requiring ultrasound (US) waves, sonosensitizing molecules, and oxygen. However, sonosensitizers such as protoporphyrin IX (PpIX) face limitations, including poor water solubility, phototoxicity, and lack of targeting. To address these issues, we encapsulated PpIX in biocompatible nanomicelles to enhance solubility, reduce side effects, and improve tumor targeting. Materials and Methods: After synthesizing, characterizing, and assessing the cytotoxicity of PpIX-loaded nanomicelles, the optimal concentration was selected. The 4T1 cell line was used to create a breast tumor model in BALB/c mice. To investigate the effect of SDT mediated by PpIX-loaded nanomicelles, tumors were exposed to US at 800 and 2400 kHz simultaneously, 10 min after intratumoral injection of the drug. The tumors were measured with a digital calliper, and tumor volume was calculated at specific time intervals and compared. The tumor tissue necrosis percentage was determined by pathological examination, and the volume loss in different groups was quantified. Results: SDT with PpIX nanomicelles significantly reduced tumor volume within 7 days compared with controls ( Conclusion: PpIX-loaded nanomicelles enhance SDT efficacy in breast tumors, demonstrating potential as a targeted delivery system. Repeated treatments may further inhibit tumor growth.