The aim of this study was to develop a suitable drug delivery system without Tween 80 and design docetaxel (DTX)-loaded PLA-PEG nanoparticles to improve solubility and decrease side effect of docetaxel. DTX-loaded PLA-PEG nanoparticles were prepared by modified solvent volatilixation method and characterized by particle size distribution, zeta potential and entrapment efficiency. The morphology of DTX loaded PLA-PEG nanoparticles was approximately spherical. The mean diameter and zeta potential of freeze-dried PLA-PEG nanoparticles were 205 +/- 8.1 nm and -24.17 +/- 2.20 mV, respectively. The average entrapment efficiency and drug loading of freeze-dried DTX-loaded PLA-PEG nanoparticles were 91.83 +/- 1.28% and 8.17 +/- 0.35%, respectively. The in vitro release showed that the release from DTX loaded PLA-PEG nanoparticles was slower than from Duopafei and followed the Weibull equation. Cytotoxicity of Duopafei and DTX loaded PLA-PEG nanoparticles was evaluated. Compared with Duopafei, DTX-loaded PLA-PEG nanoparticles showed similar cytotoxicity against three human cancer cell lines and lower toxicity on human normal hepatocellular HL-7702 cells. The apoptosis was detected and measured with Hoechst 33342 and AnnexinV-FITC kit. Compared with Duopafei, DTX-loaded PLA-PEG nanoparticles revealed similar cytotoxicity against A549 cells by inducing similar apoptosis. These results indicated that the PLA-PEG nanoparticles obtained in this study could potentially be exploited as a carrier without Tween 80, which improved drug solubility and decrease side effect of docetaxel.