Therapeutic nanoparticles (NPs) based on the donor-acceptor-donor structured small organic molecule diketopyrrolopyrrole (SDPP) were prepared using a simple reprecipitation approach. These near-infrared radiation-absorbing NPs have high photothermal conversion efficiency and are able to selectively target cancer tissues through the enhanced permeability and retention effect. Benefiting from these advantages, SDPP NPs can serve as an excellent therapeutic agent for highly efficient and noninvasive photoacoustic imaging-guided photothermal therapy. Experiments using mouse tumor models showed that the SDPP NPs exhibited exceptional tumor ablation ability under laser irradiation (660 nm, 1.0 W·cm^-2), even at a low dose (0.16 mg·kg^-1).