Cancer is the leading cause of death worldwide. Nanomaterials and nanotechnologies could provide potential solutions. In this research, a novel biodegradable poly(lactide-co-glycolide)-d-a-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) random copolymer was synthesized from lactide, glycolide and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) by ring-opening polymerization using stannous octoate as catalyst. The obtained random copolymers were characterized by 1H NMR, FTIR, GPC and TGA. The docetaxel-loaded nanoparticles made of PLGA-TPGS copolymer were prepared by a modified solvent extraction/evaporation method. The nanoparticles were then characterized by various state-of-the-art techniques. The results revealed that the size of PLGA-TPGS nanoparticles was around 250 nm. The docetaxel-loaded PLGA-TPGS nanoparticles could achieve much faster drug release in comparison with PLGA nanoparticles. In vitro cellular uptakes of such nanoparticles were investigated by CLSM, demonstrating the fluorescence PLGA-TPGS nanoparticles could be internalized by human cervix carcinoma cells (HeLa). The results also indicated that PLGA-TPGS-based nanoparticles were biocompatible, and the docetaxel-loaded PLGA-TPGS nanoparticles had significant cytotoxicity against Hela cells. The cytotoxicity against HeLa cells for PLGA-TPGS nanoparticles was in time- and concentration-dependent manner. In conclusion, PLGA-TPGS random copolymer could be acted as a novel and promising biocompatible polymeric matrix material applicable to nanoparticle-based drug delivery system for cancer chemotherapy.