Abstract Glioma is the most frequent primary brain tumour of the central nervous system. Its high aggressiveness and deep‐seated brain lesion make it a great challenge to develop a non‐invasive, precise and effective treatment approach. Here, we report a multifunctional theranostic agent that can integrate imaging and therapy into a single nano‐platform for imaging‐guided sonodynamic therapy ( SDT ). The SDT agents were fabricated by encapsulation of sinoporphyrin sodium ( DVDMS ) chelating with manganese ions into nanoliposomes ( DVDMS ‐Mn‐ LP s). DVDMS ‐Mn‐ LP s are physiologically stable and biologically compatible, and they can produce singlet oxygen upon ultrasound irradiation to kill cancer cells. Both cell and animal studies demonstrated that SDT with DVDMS ‐Mn‐ LP s can significantly improve the antitumour growth efficiency even in the presence of skull. In addition, DVDMS ‐Mn‐ LP s are good for MR and fluorescence imaging. Thus, DVDMS ‐Mn‐ LP s reported here may provide a promising strategy for imaging‐guided modality for glioma treatment.