Acoustic inertial cavitation (IC) is a crucial phenomenon for many ultrasound (US)-related applications. This study aimed to investigate the roles of textural and surface properties of NPs in IC generation by combining typical IC detection methods with various types of silica model NPs. Acoustic passive cavitation detection, optical high-speed photography, and US imaging have been used to quantify IC activities (referred to as the IC dose, ICD) and describe the physical characteristics of IC activities from NPs. The results showed that the ICDs from NPs were positively correlated to their surface hydrophobicity and that their external surface hydrophobicity plays a much more crucial role than do the textural properties. The high-speed photography revealed that the sizes of IC-generated bubbles from superhydrophobic NPs ranged from 20-40 μm at 4-6 MPa and collapsed in several microseconds. Bubble clouds monitored with US imaging showed that IC from NPs was consistent with the surface hydrophobicity. The simulation results based on the crevice model of cavitation nuclei correlated well with the experimental results. This study has demonstrated that the surface property, instead of the textural property, of NPs dominated the IC generation, and surface nanobubbles adsorbed on the NP surface have been proposed to be cavitation nuclei.