A theranostic system of image-guided phototherapy is considered as a potential technique for cancer treatment because of the ability to integrate diagnostics and therapies together, thus enhancing accuracy and visualization during the treatment. In this work, we realized photoacoustic (PA) imaging-guided photothermal (PT)/photodynamic (PD) combined cancer treatment just via a single material, MoO3−x quantum dots (QDs). Due to their strong NIR harvesting ability, MoO3−x QDs can convert incident light into hyperthermia and sensitize the formation of singlet oxygen synchronously as evidenced by in vitro assay, hence, they can behave as both PT and PD agents effectively and act as a “dual-punch” to cancer cells. In a further study, elimination of solid tumors from HeLa-tumor bearing mice could be achieved in a MoO3−x QD mediated phototherapeutic group without obvious lesions to the major organs. In addition, the desired PT effect also makes MoO3−x QDs an exogenous PA contrast agent for in vivo live-imaging to depict tumors. Compared with previously reported theranostic systems that put several components into one system, our multifunctional agent of MoO3−x QDs is exempt from unpredictable mutual interference between components and ease of leakage of virtual components from the composited system.