For effective therapy for glioma, it is essential for chemotherapeutics to pass the blood-brain barrier to target glioma cells with little side effects to surrounding normal cells. In this study, we prepared doxorubicin-polybutylcyanoacrylate nanoparticles (Dox-PBCA-NP) and assessed its inhibition effects on glioma both in vitro and in vivo. Dox-PBCA-NP was prepared using the emulsion polymerization method. The size and size distribution of nanoparticles were measured by Malven laser mastersizer and the morphology was observed under transmission electron microscope. Drug loading (DL) and entrapment efficiency (EE) of doxorubicin in the nanoparticles were measured by UV spectra. The proliferation of C6 glioma cells was detected by MTT assay, and cell cycle was analyzed by flow cytometry. The expression of telomerase was detected by immunocytochemical analysis. The anti-tumor efficiency of Dox-PBCA-NP was assessed in C6 glioma intracranial implant rat model. The average diameter of NP-Dox was 120?nm, DL was 10.58?%, and EE was 87.43?%. We found that the cytotoxicity of Dox-PBCA-NP was lower than Dox in vitro. In vivo, Dox-PBCA-NP could transport more Dox into tumors compared to contralateral control, and the life span was longer than Dox. Moreover, Dox-PBCA-NP had less cardiotoxicity than Dox. Taken together, our results suggest that Dox-PBCA-NP exhibits better therapeutic effects against glioma and fewer side effects and is a potential nano-scale drug delivery system for glioma chemotherapy.