Paclitaxel (Ptx), a microtubule depolymerization inhibitor, is one of the first-line regimens in lung cancer chemotherapy. However, the poor solubility of Ptx, as well as hypersensitivity of the solvent Cremphor EL, severely limits its clinical application. Here we developed a drug-polymer conjugate of Ptx-SA-PEG, in which amphiphilic copolymers poly(ethylene glycol) (PEG) and Ptx were conjugated by succinic acid (SA). The Ptx-SA-PEG polymers self-assemble into nanoparticles (Ptx-NPs) for efficient delivery of Ptx; cell count kit-8 assay and clonogenic assay were used to analyze the antitumor effect of Ptx-NPs. Acridine orange/ethidium bromide double staining, apoptosis analysis and western blot were measured to explore the apoptotic cell death after Ptx-NPs or free Ptx treatment. Subcutaneous xenograft models were practiced to estimate its tumor cytotoxicity and nonspecific side effects in vivo . Immunohistochemistry was used to analyze the effects of apoptosis and proliferation in tumor tissue; in vitro studies demonstrated that Ptx-NPs treatment exhibited more tumor inhibitory activity compared with free Ptx, especially at the lower doses. Moreover, Ptx-NPs activated apoptotic proteins. Animal experiments showed Ptx-NPs induced less weight loss and organ damage than free Ptx. Moreover, tumor growth was slower after Ptx-NPs treatment, indicating the superior antitumor effect and slight side effect of Ptx-NPs over free Ptx. Conjugation of Ptx-SA-PEG provides a feasible way to acquire self-assembled supramolecular Ptx-loaded nanoparticles with higher drug loading efficiency, less non-specific toxicity and more stable and durable antitumor effect of Ptx, providing a potential strategy to meliorate its clinical therapeutic efficacy.