Organic photosensitizers (PSs) possessing NIR-II emission and photodynamic/photothermal effect have received a great sense of attention for their cutting-edge applications in imaging-guided multimodal phototherapy. However, it is highly challenging to design efficient PSs with high luminescence and phototherapy performance simultaneously. In this study, a spiro-functionalization strategy is proposed to alleviate aggregate-caused quenching of PSs and promote photodynamic therapy, and the strategy is verified via a spiro[fluorine-9,9'-xanthene]-modified NIR-II PS (named SFX-IC) with an acceptor-donor-acceptor configuration. SFX-IC-based nanoparticles (NPs) display a high molar extinction coefficient of 7.05 × 10