Sonodynamic therapy (SDT) has been more attractive to carry out oncology treatments in recent years. However, imaging-guided sonodynamic therapeutic nanomedicine is still a shortage in SDT development. In this work, we designed and fabricated an organic SDT system based on combination of 1,2,4,5-tetrakis(4-carboxyphenyl)-porphyrin (TCPP) and gadolinium(III) (Gd³⁺) creatively (Gd-PPNs). Gd³⁺ was traditionally used to be T₁-weighted magnetic resonance imaging (MRI) contrast agent and TCPP was initiatively a fluorescence imaging organic media. Therefore, these new designed nanoparticles have immense potential to integrate MRI and FLI to visualize the Gd-PPNs accumulating and keeping in tumor for a long time, which could be applied for guidance of SDT on tumors in clinical practice. Importantly, excellent SDT efficiency under imaging guidance was verified both in vitro and in vivo in this work. Our findings suggested that Gd-PPNs, as innovative imaging and therapy combinational nanomedicines, were successfully synthesized and were proved to possess excellent imaging-guided sonodynamic therapeutic efficacy. Moreover, this new designed sonosensitizer had great biocompatibility to avoid unnecessary biotoxicity. Overall, this strategy shed light on the MRI/FLI-guidance and successfully induced pancreatic tumor growth inhibition by sonodynamic therapy.