Radiotherapy and chemotherapy are both common clinical treatment methods. The combination of the two treatments can decrease tumor recurrence. In this study, bismuth-based mesoporous litchi shaped NaBiOF:20%Yb (NBOF) nanoparticles (NPs) have been reported as a radiosensitizer and as a nano-vehicle for loading and slow releasing doxorubicin (DOX). After assembling with amphiphilic polyethylene glycol (PEG), NBOF-DOX-PEG qualified excellent aqueous dispersibility and the enhanced tumor radiation and chemo-synergistic therapy characteristics. The formation of NBOF revealed the oxygen element in NBOF came from HO and air in the synthesis and post-treatment process, and the size of NBOF could be adjusted by changing the concentration of doped Yb ion. The average size of NBOF was ca. 80 nm. The BET results demonstrated the mesoporous structure of NBOF. So DOX could be loaded in NBOF and the optimized loading content was 39%. Then, NBOF-PEG exhibited strong CT signal whitening ability and enhanced radiotherapy effect. Combined with chemotherapy ability of DOX, NBOF-DOX-PEG NPs presented remarkable synergistic tumor elimination ability. Meanwhile, NBOF-DOX-PEG NPs qualified excellent biosafety. Our study not only proved the combined chemo and radiotherapy for enhancing therapeutic effect, but also supplied a functional Bi-based mesoporous nano-vehicle for constructing intelligent theranostic platform.