Mechanical high-intensity focused ultrasound (HIFU) has been used for cancer treatment and drug delivery. Existing monitoring methods for mechanical HIFU therapies such as MRI and ultrasound imaging often suffer from high cost, poor spatial-temporal resolution, and/or low sensitivity to tissue’s hemodynamic changes. Evaluating vascular injury during mechanical HIFU treatment, therefore, remains challenging. Photoacoustic computed tomography (PACT) is a promising tool to meet this need. Intrinsically sensitive to optical absorption, PACT provides high-resolution imaging of blood vessels using hemoglobin as the endogenous contrast. In this study, we have developed an integrated HIFU-PACT system for detecting vascular rupture in mechanical HIFU treatment. We have demonstrated singular value decomposition for enhancing hemorrhage detection. We have validated the HIFU-PACT performance on phantoms and in vivo animal tumor models. We expect that PACT-HIFU will find practical applications in oncology research using small animal models.