Public awareness of the toxicity of volatile organic compounds (VOCs) has led to increased requirements for direct measurement of these substances. This work reports the sensitive detection of VOCs at the ppb level by an interferometric sensor based on the multilayer silica-nanochannel membrane (MSNM). The MSNM is fabricated by layer-by-layer stacking of a free-standing ultrathin SNM composed of regularly ordered channels with an ultrasmall diameter of about 2.3 nm and an ultrahigh density of about 4 × 1012 cm-2. Light reflected from parallel interfaces of the MSNM gives rise to the interferometric pattern with constructive and destructive fringes. The adsorption of VOCs to a highly porous MSNM varies the refractive index of the MSNM, resulting in the shift of the reflectometric interference spectrum (RIS) and thus yielding highly sensitive responses with a limit of detection (LOD) at the ppb level. Moreover, the sensor selectively responds to polar ethanol and acetone, as well as aromatic benzene, toluene, and chlorobenzene, but is insensitive to nonpolar ethane or hexane. The selectivity most likely arises from hydrogen bonding and dipole interaction of VOCs with silica surface.