Background:　Sono-photodynamic　therapy　(SPDT)　which　is　the　combination　of　photodynamic　therapy　(PDT)　and　sonodynamic　therapy　(SDT),　could　exert　much　better　anti-cancer　effects　than　monotherapy.　The　combination　of　chemotherapy　and　PDT　or　SDT　has　shown　great　potential　for　cancer　treatment.　However,　the　combination　of　SPDT　and　chemotherapy　for　cancer　treatment　is　rarely　explored.　Purpose:　We　utilized　a　natural　hydrophobic　anti-cancer　drug　oleanolic　acid　(OA)　and　a　photosensitizer　chlorin　e6　(Ce6)　through　self-assembly　technology　to　form　a　carrier-free　nanosensitizer　OC　for　combined　chemotherapy　and　SPDT　for　cancer　treatment.　No　studies　involving　using　carrier-free　nanomedicine　for　combined　chemotherapy/　SPDT　have　been　reported　yet.　Study　design:　After　fully　characterization　of　OC,　the　in　vitro　and　in　vivo　anti-cancer　activities　of　OC　were　investigated　and　the　mechanisms　of　the　synergistic　therapeutic　effects　were　studied.　Methods:　OC　were　synthesized　through　self-assembly　technology　and　characterized　by　dynamic　light　scattering　(DLS)　and　an　atomic　force　microscope　(AFM).　Confocal　microscope　was　used　to　investigate　the　intracellular　uptake　efficiency　and　the　penetration　ability　of　OC.　The　cell　viability　of　PC9　and　4T1　cells　treated　with　OC　under　laser　and　ultrasound　(US)　irradiation　was　determined　by　MTT　assay.　Furthermore,　flow　cytometry　was　performed　to　detect　the　reactive　oxygen　species　(ROS)　generation,　loss　of　mitochondrial　membrane　potential　(MMP),　cell　apoptosis　and　cell　cycle　arrest.　Finally,　the　anti-tumor　therapeutic　efficacy　of　OC　was　investigated　in　orthotopic　4T1　breast　tumor-bearing　mouse　model.　Results:　OC　showed　an　average　particle　size　of　around　100　nm　with　excellent　light　stability.　OC　increased　more　than　23　times　accumulation　of　Ce6　in　cancer　cells　and　had　strong　tumor　penetration　ability　in　three-dimensional　(3D)　multicellular　tumor　spheroids　(MCTSs).　Compared　with　other　therapeutic　options,　OC　showed　obvious　synergistic　inhibitory　effects　under　light　and　US　irradiation　in　PC9　and　4T1　cells　with　a　significant　decrease　in　IC50　values.　Mechanism　studies　showed　that　OC　could　generate　high　ROS,　induce　MMP　loss,　and　cause　apoptosis　and　cell　cycle　arrest.　In　vivo　studies　also　approved　the　synergistic　therapeutic　effects　of　OC　in　4T1　mouse　models.　Conclusion:　Self-assembled　carrier-free　nanosensitizer　OC　could　be　a　promising　therapeutic　agent　for　synergistic　chemo/sono-photodynamic　therapy　for　cancer　treatment.