The aim of the present study was to develop a polymeric delivery system for water-insoluble drug oridonin. Amphiphilic block copolymers, poly(epsilon-caprolactone)-poly(ethylene glycol)-poly (epsilon-caprolactone) (PCL-PEO-PCL), were synthesized by ring-opening polymerization of caprolactone initiated by the hydroxyl groups of poly(ethylene glycol)6000 (PEG-6000) with stannous octoate as catalyzer. Oridonin-loaded PCL-PEO-PCL copolymer nanoparticles (ORI-PCL-PEO-PCL-NPs) were prepared by the interfacial deposition method. The mean particle size of the drug-loaded nanoparticles was 97.5 nm and the zeta potential was - 25 mV. The entrapment efficiency and actual drug loading of the nanoparticles were 87.52% +/- 1.86% and 8.63% +/- 0.49%, respectively. The antitumor activity of ORI-PCL-PEO-PCL-NPs was evaluated by measuring changes in tumor volumes, tumor weights, and survival rates of mice with grafted hepatoma (H22). The results indicated that ORI-PCL-PEO-PCL-NPs prolonged the survival time of mice and exhibited higher therapeutic efficacy compared with free oridonin. Thus, ORI-PCL-PEO-PCL-NPs may be used as a promising delivery system for liver cancer treatment.