Aggregation profoundly influences the photophysical properties of molecules. Here, a new series of thiopyrylium-based hemicyanine near-infrared II (NIR-II) fluorophores is developed by meticulously adjusting their aggregation states. Notably, the star molecule HTPA exhibits a remarkable pH-responsive behavior and a significant increase in photoacoustic (PA) intensity when aggregated. Additionally, their behavior and pH reversibility during aggregation formation are systematically investigated, including computational optimization, femtosecond transient absorption spectroscopy, NMR analysis, and single crystal analysis. Finally, an innovative "off " nanoparticle specifically is designed for effective tumor-targeted PA/NIR-II dual-modal imaging and photodynamic therapy by utilizing a pH-responsive polymer. The signal-to-background ratio (SBR) of PA signals significantly increased to 169 in the region of interest (ROI) in the mouse model when irradiated at 1064 nm. These findings not only provide a promising avenue for future studies of NIR-II small molecules but also pave the way for significant advances in the field of integrated cancer diagnosis and therapy.