Magnetic nanoparticles have gained much interest for theranostics benefited from their intrinsic integration of imaging and therapeutic abilities. Herein, c(RGDyK) peptide PEGylated Fe@Fe3 O4 nanoparticles (RGD-PEG-MNPs) are developed for photoacoustic (PA)-enabled self-guidance in tumor-targeting magnetic hyperthermia therapy in vivo. In the αv β3 -positive U87MG glioblastoma xenograft model, the PA signal of RGD-PEG-MNPs reaches its maximum in the tumor at 6 h after intravenous administration. This signal is enhanced by 2.2-folds compared to that of the preinjection and is also 2.2 times higher than that in the blocking group. It demonstrates the excellent targeting property of RGD-PEG-MNPs. With the guidance of the PA, an effective magnetic hyperthermia to tumor is achieved using RGD-PEG-MNPs.