Lots of efforts have been devoted to enhancing the antitumor efficacy of reactive oxygen species (ROS)-responsive nanoscale drug delivery systems. Here, a ROS-responsive amphiphilic polymer (mPEG-b-poly(thioacetal-thioether), P2) with property of generation and self-sustained high level of ROS, and a control material mPEG-b-poly(ester-thioether) (P1) were constructed and characterized by proton nuclear magnetic resonance ( 1 H NMR). The two polymers could self-assemble into micelles and the doxorubicin loading content of P1 and P2 micelles were 13.08 % and 13.51 %, respectively. The two polymers could self-assemble into micelles and exhibit good DOX loading capacity. ROS-responsiveness of P1 and P2 micelles was investigated by 1 H NMR, dynamic light scattering (DLS), and scanning electron microscope (SEM). The results of in vitro ROS detection indicated that P2 micelles could ROSresponsive release of cinnamaldehyde, and promote intracellular generation of ROS and maintain high level of ROS. DOX/P1 micelle shown comparable in vitro antitumor efficacy with DOX/P2 micelle, and a slightly lower IC50 value was due to DOX/P1 micelle has faster cell internalization, poorer micelle stability and integrality. Considering the stability of the nanoparticle circulation in vivo, the DOX/P2 micelle containing both thioether and thioacetal would be more suitable and could show better in vivo antitumor efficacy.