Abstract: The aim of this study was to prepare the nanoconjugates for targeted photodynamic therapy of brain cancer by using eight-arm polyethylene glycol(8PEG)as the carrier and cRGD as the targeting ligand, and to investigate the antitumor effect and its mechanism. UV-Vis spectra and confocal microscopy were used for characterization and cellular uptake behavior of nanoconjugates respectively. Alamar Blue assay and Calcein AM/PI staining were applied to investigate the cytotoxocity of nanoconjugates against tumor cells, and tumor spheroid growth curve was used to assess the tumor growth suppression effect. In addition, the generation of reactive oxygen species(ROS), apoptosis and spheroid permeability test was used to reveal the antitumor mechanism of nanoconjugates. The results showed that cRGD-8PEG-IR700 was taken up efficiently by integrin overexpressed U87MG cells, while almost no uptake was found in integrin free NIH/3T3 cells. Remarkable photokilling effect against U87MG cells was only shown in cRGD-8PEG-IR700 group due to the light-induced ROS generation and apoptosis, whereas growth suppression effect was also observed in U87MG spheroids treated with cRGD-8PEG-IR700 plus light owing to the superior penetration ability of targeted nanoconjugates. Hence, tumor-targeted PEG nanoconjugates may provide a promising drug delivery system for photodynamic therapy of cancers.