Serious hypoxia in solid tumor as well as vicious aggregation-caused fluorescence quenching (ACQ) of conventional photosensitizers (PSs) limit the progress of the fluorescence imaging-guided photodynamic (PDT) although it has obvious advantages in precise spatial-temporal control and noninvasive treatment. The photosensitizers featuring Type I reactive oxygen species (ROS) based on free radical and novel aggregation-induced emission (AIE) characteristic (AIE-PSs) could offer precious opportunity to resolve above problems, but there was rare feasible molecular engineering in previous reports. Herein, we proposed that the strategy of fabricating stronger intermolecular charge transfer (ICT) effect in electron-rich anion-π+ AIE-active luminogens (AIEgens) aimed to help suppressing nonradiative internal conversion (IC) as well as promote radiative and intersystem crossing (ISC) processes for boosting more free radical generation. Systematic and detailed experimental and theoretical calculations proved our ideas when the electron-donating abilities enhanced in collaborative donors, and the AIE-PSs exhibited higher performance in near-infrared red (NIR) fluorescence image-guided cancer PDT in vitro/vivo. This work would become an important reference to the design of AIE-active free radical generators for overcoming ACQ effect and tumor hypoxia in future PDT.