To improve the sonodynamic therapy (SDT) effects, hematoporphyrin monomethyl ether (HMME)-loaded liposome was developed as an ultrasound-sensitive liposome for HMME targeted delivery and specify release. The release of HMME was successfully triggered by the irradiation of ultrasound. With the help of the liposome, HMME entered the nucleus while free HMME mainly localized in the cytoplasm. Besides, the liposome significantly reduced the dark cytotoxicity of HMME, while improving the SDT effect.