Helicobacter pylori is a causative factor of various gastrointestinal tract diseases. As clinical antibioticbased therapy for H. pylori infection might induce bacterial drug resistance, the in vivo eradication of H. pylori remains a huge challenge. In the present study, monoclonal antibody-conjugated liposomes loaded with indocyanine green (ICG) ( Hp Ab-LiP-ICG) were successfully developed for targeted photoacoustic (PA) imaging-guided sonodynamic therapy (SDT) of H. pylori infection in vivo. Hp Ab-LiP-ICG showed high stability and favorable biocompatibility in acidic environment (pH 1.5) and was used for treating H. pyloriinfected mice through oral administration. PA imaging showed that Hp Ab-LiP-ICG could precisely recognize and target H. pylori in the stomach. Following the targeting of Hp Ab-LiP-ICG to H. pylori , ICG was activated to generate singlet oxygen ( 1 O 2 ) for eliminating H. pylori under ultrasound (US) irradiation. Pathological analysis revealed that the Hp Ab-LiP-ICG-mediated SDT eradicated H. pylori without unintended toxicity to normal tissues. In conclusion, the Hp Ab-LiP-ICG-mediated SDT might shed new light on treating H. pylori infection, indicating the clinical translational prospects of this therapy in near future.