The use of radiotherapy sensitizers has proven to be effective in overcoming tumor radiotherapy resistance and improving treatment efficacy. However, challenges such as poor biocompatibility and difficulty in accurately guiding tumor radiotherapy with high efficiency still persist. Herein, we propose a radiosensitizer with Janus nanostructure to address these issues by enabling dual-modal fluorescence (FL)/photoacoustic (PA) imaging in the second near-infrared region (NIR-II, 900-1700 nm) for precise and efficient tumor radiotherapy guidance. The Janus nanoprobes are fabricated by initially coating silica (SiO) on one end of gold nanorod (AuNR) with a high aspect ratio, followed by decoration of a lanthanide-doped down-conversion nanoparticle (DCNP) shell on SiO, and finally modifying it with biocompatible polyethylene glycol (PEG), named as AuNR@DCNP@PEG. Guided by NIR-II FL/PA imaging, AuNR@DCNP@PEG was successfully irradiated at the optimal tumor enrichment time point, generating a significant amount of reactive oxygen species and exhibiting excellent sensitization effects and . This dual-modal NIR-II FL/PA imaging-guided radiotherapy sensitizer is anticipated to offer an approach for overcoming radiotherapy resistance and achieving precise and efficient radiotherapy.