Amphiphilic nanoparticles are known to cause defects in lipid bilayers. However, we have shown recently that their disruptive effects are significantly enhanced when surface charges and hydrophobic groups are spatially segregated on opposite hemispheres of a single particle. Using the same amphiphilic cationic/hydrophobic Janus particle system, here we investigate the role of the hydrophilic-lipophilic balance of the particles (namely the Janus balance) in their interaction with zwitterionic lipid bilayers. We show that Janus nanoparticles induce holes in lipid bilayers only when the hydrophobic side of particles occupies 20% or more of their surfaces. Beyond this threshold, the larger the hydrophobic surface area, the more attractive the particles are to lipid bilayers, and a lower particle concentration is needed for causing defects in the bilayers. The results establish a quantitative relationship between the surface coverage of hydrophobicity on the Janus particles and the particle-induced disruption to the lipid membranes.