Silicon nanoparticles (NPs) are widely used nanomaterials and reported to have pathogenicity. Effects of five different SiO2 NPs on the membrane integrity and fluidity were studied using giant unilamellar vesicles (GUVs) as model cell membranes. GUVs were made from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) by gentle hydration method, and adjusted to be positively- or negatively-charged by adding charged lipids into vesicles. SiO2 NPs caused more serious damage to oppositely-charged membrane because electrostatic attraction favored the hydrogen bonding to the phospholipids. Increase in NP exposure dose/time and NP sedimentation process aggravated the membrane damage. The membrane phases were evaluated applying the fluorescent probe Laurdan and the calculated generalized polarization (GP) values. Anionic SiO2 NPs increased the GP value and induced membrane gelation. Cationic SiO2 NPs did not change the phase of positively-charged GUV and pure DOPC vesicles, but induced the gelation of negatively-charged GUV. Break of membrane integrity and change in membrane phase are possible mechanisms of cytotoxicity because cellular physiological activities require a separated intracellular environment and a fluid membrane phase to support proteins and regulate molecular transport. (C) 2015 Elsevier B.V. All rights reserved.