Photodynamic therapy (PDT) is a new minimally invasive technology for disease diagnosis and treatment. However, the biological tissue attenuation of visible light renders the depth of its penetration in tissues quite modest, which significantly restricts its therapeutic applicability. Therefore, it is an essential but yet a difficult task to enhance the X-ray sensitization impact while concurrently limiting the tissue scattering by the rational design of novel biological vectors. Herein, a novel Lu3Al5O12:Mn/Ca-Ce6@SiO2 nanoparticle system (LAMCCS) based on a pea-shaped LuAG:Mn/Ca nano-scintillator (LAMC) activating photosensitizer agent (Ce6) was designed. Due to the high radiosensitization of LAMC nano-scintillators and efficient energy conversion efficiency between LAMC and Ce6, more singlet oxygen (1O2) could be generated to efficiently damage DNA fragments and reveal a good effect of inhibiting the long-term proliferation of tumor cells in vitro. Significantly, synergistic therapy with PDT/radiotherapy (RT) and from LAMCCS nanocomposites may still maintain a high tumor growth inhibition rate of 72% than single RT of 10% in vivo. Owing to their excellent ability for X-ray sensitization and energy conversion, LAMCCS nanocomposites may have significant tumor growth suppression rates under lower X-ray dose irradiation due to their outstanding X-ray sensitization and energy conversion capabilities, which may open up a new avenue for the advancement of cancer therapy.