The efficiency of sonoporation, a phenomenon where acoustic-responsive nanomaterials create transient pore on cell membrane to deliver therapeutic cargoes to cell cytosol, remains difficult to predict. As a result, many clinical applications involving sonoporation faces critical issue in reliability. Herein, we hypothesized that sonoporation efficiency is depending on viscoelasticity of surrounding microenvironment. By using experimental methods, such as flow cytometry, fluorescent microscopy, we established relationship between membrane elasticity and sonoporation efficiency for the first time.