ABSTRACTPurpose: The purpose of this study was to evaluate the sonodynamically induced antitumor effect of a novel sonosensitizer (DVDMS) in mice bearing sarcoma 180 solid tumors. Methods: In order to determine the optimum timing of ultrasound exposure after administration of DVDMS, a three‐dimensional optical imaging system (IVIS spectrum) was used to observe the biodistribution of DVDMS in S180 tumor. The antitumor effects were estimated by the tumor inhibition ratio (volume and weight) after sonodynamic therapy. Results: The experiments suggested that DVDMS has a preferential localization in tumors, but a low accumulation in most normal tissues. A significant synergistic effect of ultrasound combined with DVDMS was obtained when the load power indicated 4 W and DVDMS dose was above 2 mg/kg. At day 14 after DVDMS‐SDT, the tumor volume inhibition ratio was 56.27%. In addition, the tumor weight inhibition ratio after the synergistic treatment was 55.37%, which was obviously stronger than ultrasound treatment alone (23.85%) and DVDMS alone (23.15%). Moreover, no metastasis occurred to the tumors in the SDT‐treated mice compared with the control group. Conclusions: DVDMS is a potential sensitizer for sonodynamic cancer therapy. The antitumor effect of ultrasound could be enhanced in the presence of DVDMS, which might be involved in a sonochemical mechanism. Copyright © 2013 John Wiley & Sons, Ltd.