The invention discloses a composite nanoparticle for sensitizing tumor radiotherapy and a preparation method and application of the composite nanoparticle. The composite nanoparticle comprises proteinand bismuth selenide and manganese dioxide which grow on the protein. The preparation method comprises the steps that a manganese salt solution is added into a aqueous dispersion of bismuth selenide-protein nanoparticles, after uniform mixing is carried out, a strong alkaline solution is added, the pH value is adjusted to alkaline, a heating temperature control reaction is carried out, ultrafiltration and washing are carried out, and the composite nanoparticle is obtained. The composite nanoparticle has the advantages that the water dispersibility and biocompatibility are good, radiotherapy is sensitized by increasing the local radiation dosage through bismuth selenide and improving tumor hypoxia through manganese dioxide, and computed tomography, magnetic resonance and photoacoustic multimode imaging angiography can be achieved simultaneously; the preparation method of the composite nanoparticle is simple, convenient and practical, the condition is mild, the controllability is good,and the implementation and promotion are easy; the composite nanoparticle can achieve the integration of targeted radiotherapy sensitization, diagnosis and treatment of the tumor, and has a broad application prospect in the fields of nano-medicine, disease diagnosis, tumor treatment and the like.