The interaction of nanoparticles with cell membranes is critical to understand and control the structural change and molecular transport of cell membranes for medicines and medical diagnostics, in which hydrophobic interaction is often involved. We examine the specific ion effect on the interaction of semihydrophobic nanoparticle with zwitterionic phospholipid bilayer in aqueous media added with different types of salts. Specifically, we compare the effect of different anions or cations on the adsorption of carboxyl-functionalized polystyrene nanoparticle on supported lipid bilayer and its induced bilayer disruption. By adding different anions at the same ionic concentration to the nanoparticlelipid bilayer interface, we observe that the growth rate of nanoparticle-induced lipid-poor regions follows the exact Hofmeister anion order of CH3COO > Cl > NO3 >> SCN , suggesting the regulated hydrophobic interaction by anions. In contrast, the specific cation effect on nanoparticle-induced disruption rate of lipid bilayer does not follow the Hofmeister cation order and instead exhibits a trend of Cs+ similar to Rb+ > Na+ >> N(CH3)(4)(+). It is suggested that the effect of specific ions can be exploited as a simple and efficient approach to modify the nanoparticlesbiomembrane interactions with the implication from drug delivery to nontoxic nanomaterial design.