Enhancing the phototherapy efficacy of organic photosensitizers through molecular design is a fascinating but challenging task. Herein, we propose a simple design strategy to first realize the generation of superoxide anion radical (O 2 •- ) by A-D-A fused-ring photosensitizers. Through replacing one cyano group of traditional end group with an ester group, we designed a novel nonplanar end group (A unit) to synthesize a novel A-D-A photosensitizer F8CA. In a comparison with its counterpart F8CN with the traditional end group, F8CA displays more loose packing and larger spin-orbit coupling constants. The F8CA nanoparticles showed higher photodynamic activities with the generation capability of singlet oxygen ( 1 O 2 ), hydroxyl radical ( • OH), and O 2 •- , while F8CN nanoparticles could only generate 1 O 2 and • OH. In addition, F8CA nanoparticles still remain high photothermal conversion efficiency (61%). As a result, F8CA nanoparticles perform well in hypoxia-tolerant tumor phototherapy. This study brings an effective design thought for A-D-A photosensitizers.