The　selective　separation　and　detection　of　benzene　from　toluene　remains　a　critical　challenge　due　to　their　structural　similarity　and　the　toxicity　of　benzene.　In　this　work,　we　develop　a　novel　composite　substrate,　PIZA-AgNW,　consisting　of　a　metal-organic　framework　(MOF),　silver　nanowires　(AgNWs),　and　filter　paper,　fabricated　via　liquid-phase　epitaxy　(LPE).　This　substrate　enables　highly　selective　and　real-time　detection　of　benzene　from　toluene　using　tandem　surface-enhanced　Raman　spectroscopy　(SERS)　and　quartz　crystal　microbalance　(QCM)　analysis.　The　LPE　method　affords　precise　control　of　MOF　thickness　and　pore　structure,　enhancing　molecular　selectivity　for　Raman　detection.　By　correlating　Raman　intensity　with　QCM-derived　mass　changes,　we　achieve　real-time　monitoring　of　adsorption/desorption　dynamics　and　quantify　both　equilibrium　and　nonequilibrium　separation　factors.　Notably,　a　high　equilibrium　separation　factor　(αₑ)　of　134　was　obtained　for　a　1:1　benzene/toluene　mixture.　This　work　demonstrates　a　practical　strategy　for　integrating　structural　selectivity　with　real-time　sensing　and　offers　broad　potential　for　the　dynamic　monitoring　of　volatile　organic　compounds　(VOCs)　in　environmental　and　industrial　applications.　©　2025　Elsevier　B.V.