OBJECTIVE: To study the role of curcumin-mediated sonodynamic therapy in the treatment of malignant melanoma, and to provide a new strategy for the treatment of malignant melanoma. METHODS: The ultrasonic sound and vibration method was applied to coat curcumin with mouse melanoma cell membrane, thereby forming biomimetic curcumin. The morphology of biomimetic curcumin was observed by transmission electron microscope. Flow cytometry was used to analyze the effect of biomimetic curcumin in terms of targeting, apoptosis, and intracellular reactive oxygen species (ROS) production. The experiment was divided into control group, US group, turmeric group, imitation turmeric group, and imitation turmeric+US group, with 3 mice in each group. The safety of biomimetic curcumin was evaluated by HE staining. In addition, HE, CD31, Ki67, and TUNEL stainings were performed to evaluate the anti-melanoma therapeutic effect of ultrasound combined with biomimetic curcumin. RESULTS: The biomimetic curcumin had a generally uniform morphology and possessed a core-shell structure. Flow cytometry analysis performed with FlowJo showed that the biomimetic curcumin could be effectively taken up by melanoma cells. The apoptosis rate was (10.30±0.61)% in the control group, (10.41±3.13)% in the ultrasound group, (24.97±1.38)% in the curcumin group, (31.39±3.84)% in the biomimetic curcumin group, and (40.89±0.79)% in the biomimetic curcumin and ultrasound combination group. The apoptosis rate in the biomimetic curcumin and ultrasound combination group was higher than those in the other groups (<0.05). The results of ROS flow cytometry showed that, compared with the control group, the ultrasound group demonstrated almost no increase in the fluorescence intensity, while the other groups showed an increase in the fluorescence intensity to varying degrees. There was no significant difference in the fluorescence intensity between the biomimetic curcumin group ([1.10±0.38]%) and the curcumin group ([0.73±0.26]%) (>0.05). The fluorescence intensity of the biomimetic curcumin and ultrasound combination group ([3.35±0.04]%) was higher than those of the other groups (<0.05). HE staining showed no obvious abnormalities in the morphology of heart, liver, spleen, lung, and kidney tissues in any of the treatment groups. HE staining showed the most significant changes in cell morphology in the biomimetic curcumin and ultrasound combination group, followed by the biomimetic curcumin group and the curcumin group. No obvious abnormalities in tumor cell morphology were observed in the ultrasound group. According to the respective results of CD31 staining, Ki67 staining, and TUNEL staining, the biomimetic curcumin and ultrasound combination group had the largest brown area, the highest number of red fluorescence, and the highest number of green fluorescence, followed by the biomimetic curcumin group and the curcumin group. CONCLUSION: The biomimetic curcumin displays uniform morphology, a core-shell structure, and good targeting properties. When it is used in combination with ultrasound, biomimetic curcumin demonstrates a good anti-tumor therapeutic effect both and .