Photochemical internalization (PCI) is a technique that uses the photochemical properties of photodynamic therapy (PDT) for the enhanced delivery of endolysosomal-trapped macromolecules into the cell cytoplasm. The released agent can therefore exert its full biological activity, in contrast to being degraded by lysosomal hydrolases. Activation of photosensitizers via ultrasound (US), called sonodynamic therapy (SDT), has been proposed as an alternative to light-activated PDT for the treatment of cancerous tumors. The use of focused US (FUS) to activate photosensitizers allows treatment at tumor sites buried deep within tissues, overcoming one of the main limitations of PDT/PCI. We have examined ultrasonic activation of photosensitizers together with the anticancer agent bleomycin (BLM) using sonochemical internalization (SCI), as an alternative to light-activated PCI. Our results indicate that, compared to drug or US treatment alone, US activation of the photosensitizer AlPcS2a together with BLM significantly inhibits the ability of treated glioma cells to form clonogenic colonies.