Small molecular nanomedicines that integrate the flexibility of self-assembly strategies and the advantages of a precise molecular structure, a high drug content and controlled drug release are effective diagnostic and therapeutic modalities. Herein, merocyanine-paclitaxel conjugates (MC-PTX) were developed and fabricated by using the degradable ester bonds as the linker. The as-prepared MC-PTX could self-assemble into nanoparticles (MC-PTX NPs) using the non-covalent molecular interaction via the nanoprecipitation method. MC-PTX NPs possess a favorable biological stability and can efficiently release the paclitaxel (PTX) activated by the heat of the photoactive material merocyanine under light illumination, as monitored using dynamic light scattering. The obtained MC-PTX NPs could be endocytosed into cancer cells and release PTX under laser irradiation in the cytoplasm, thus eliciting a satisfactory anticancer effect. Photothermal triggered degradation upon light illumination could enhance the chemotherapeutic efficacy of paclitaxel. The fluorescent nature of the NPs could visualize the internalization process. We believe that this robust nanomedicine offers a novel strategy to facilitate clinical translation for use as a small molecular chemotherapy nanomedicine.