Despite the great advances in fighting cancer, many therapies still have serious side effects, thus urging the development of highly selective and safe treatments with a wide range of applicability. Sonodynamic therapy (SDT) is an innovative bimodal anticancer approach in which two normally non-toxic components -- one chemical, a sonosensitizer, and one physical, ultrasound -- selectively combine to cause oxidative damage and subsequent cancer cell death. In this study, we investigate the anticancer effect of SDT using shock waves (SWs) to activate protoporphyrin IX (PpIX) cytotoxicity on a Mat B-III syngeneic rat breast cancer model. The SDT-treated group saw a significant decrease (p<0.001) in magnetic resonance imaging (MRI) tumor size measurements 72 hours after treatment with PpIX precursor 5-aminolevulinic acid (ALA) and SWs. This occurred together with significant increase (p<0.01) in apparent diffusion coefficients between pre- and post-treatment MR tumor maps and strong increase in necrotic and apoptotic histological features 72 hours post-treatment. Moreover, significant HIF1A mRNA expression up-regulation was observed along with the prominent selective cleavage of poly (ADP-ribose) polymerase (PARP) and increased autophagy related protein LC3A/B expression in SDT-treated tumors, as compared to untreated tumors 72 hours post-treatment. Thus, the anticancer effect of SDT can be boosted by SWs, making them a valid technology for furthering investigations into this innovative anticancer approach.