Functional polylactide-g-paclitaxel poly(ethylene glycol), a novel graft polymer drug conjugate (GPDC) with paclitaxel (PTXL) as the divalent agent to bridge between the degradable polylactide (PLA)-based backbone and hydrophilic poly(ethylene glycol) (PEG) side chains, were prepared by the copper-catalyzed azide-alkyne cycloaddition reaction of acetylene-functionalized polylactide (PLA) with azide-functionalized PTXL PEG conjugate. The acetylene-functionalized PLA was prepared by ring-opening copolymerization (ROCP) of acetylene-functionalized LA monomer with L-lactide (LA). The azide-functionalized PTXL PEG conjugate was prepared by multistep organic synthesis. The well-controlled chemical structures of the GPDC and its precursors were verified by (1)H NMR and GPC characterizations. DLS analysis indicated that GPDC molecules assembled in water to form nanoparticles with sizes of 8-40 nm. GPC analysis of buffer solutions (pH = 5.5 and 7.4) of the GPDC suggested the occurrence of multiple hydrolysis reactions under the experimental conditions, which resulted in the release of PTXL moieties and the cleavage of PLA-based backbone.