Abstract: The diblock poly(ε-caprolactone)-b-polyphosphoester (PCL-PEEP) was synthesized by ring-opening polymerization (ROP) of 2-ethoxy-2-oxo-1, 3, 2-dioxaphospholane (EOP) with PCL as macro-initiator and Sn(Oct)₂ as the ROP catalyst. Subsequently, the selenium-containing triblock polymer PCL-PEEP-Se-PEEP-PCL was synthesized by using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 4-dimethylaminopyridine as coupling catalyst and newly prepared dicarboxylic acid di-(3, 3'-carboxyl propylene) selenide (Se-DCP) as the coupling agent. As-synthezied PCL-PEEP-Se-PEEP-PCL micelles were produced after removing solvent by evaporation. The structure characteristics were confirmed by nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR) and gel permeation chromatography (GPC). The critical micelle concentration (CMC) and oxidative stimuli-response of micelles were determined by fluorescence spectroscopy, ¹H-NMR, dynamic light scattering (DLS) and transmission electron microscope (TEM). MTT assay was also applied to evaluate the biocompatibility of micelles. The results showed that the element of selenium was introduced into the polymer successfully. The CMC was determined around 0.022 mg/mL and the micelles were spherical structure with the diameter about 91 nm. The micelles disassembled and the size became irregular in the presence of H₂O₂. MTT assay revealed that the PCL-PEEP-Se-PEEP-PCL micelles had considerable biocompatibility and low cytotoxicity even the mass concentration was up to 500 μg/mL. The newly designed selenium-containing PCL-PEEP-Se-PEEP-PCL micelles with oxidation-responsive properties could provide a platform for controlled drug release toward targeted cancer therapy.