Ultrasound　(US)　imaging　is　widely　applied　in　hospital　and　clinical　settings　due　to　its　non-invasiveness,　controllability,　and　high　tissue-penetrating　ability.　Moreover,　sonodynamic　therapy　(SDT)　activated　by　US　is　a　safe　cancer　therapeutic　strategy　with　a　deep　tissue　penetration　effect.　Simultaneous　integration　of　US　imaging　contrast　agents,　controllable　drug　delivery　vehicles,　and　effective　therapeutic　drugs　in　a　single　theranostic　nanoplatform　is　a　promising　strategy　for　cancer　therapy.　Herein,　we　developed　a　2,2′-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride　(AIPH)-loaded　liposome　(Lip-AIPH)　that　can　simultaneously　generate　gas　bubbles　and　a　high　concentration　of　reactive　oxygen　species　(ROS)　under　US　irradiation.　In　vivo　experimental　results　confirmed　that　the　generated　gas　and　alkyl　radicals　were　independent　of　oxygen　generation　and　were　successfully　used　for　synergistic　gas　therapy　and　SDT　in　a　hypoxic　tumor　microenvironment.　More　importantly,　the　generated　gas　bubbles,　when　used　as　a　powerful　US　contrast　agent,　greatly　enhanced　the　US　contrast　to　guide　cancer　therapy.　As　an　US-activated　theranostic　agent,　the　liposome　enhanced　the　US　imaging　and　exhibited　an　improved　anticancer　efficacy,　and　it　may　prove　promising　for　US　imaging-guided　hypoxic　tumor　therapy　with　deep　tissue　penetration.　©　The　Royal　Society　of　Chemistry.