The　coupling　of　charge　carrier　and　phonon　transport　limits　the　application　of　Ag2Se　as　a　low-toxic　near-room-temperature　thermoelectric　material.　Strategies　that　reduce　the　thermal　conductivity　via　enhancing　the　phonon　scattering　usually　lead　to　reduced　carrier　mobility　due　to　high　grain　boundary　potential　barrier.　In　this　study,　we　developed　a　cell-membrane-mimic　grain　boundary　engineering　strategy　for　decoupling　the　charge　carrier　and　phonon　scattering　through　decorating　high-dielectric-constant　rutile　TiO2　at　Ag2Se　grain　boundaries　to　enable　the　charge　carrier/phonon　selective　permeability.　The　nano-sized　TiO2　with　high　dielectric　permittivity　can　secure　the　charge　carrier　transport　by　shielding　the　interfacial　Coulomb　potential　to　lower　the　energy　barrier　of　grain　boundaries,　rendering　an　enhanced　power　factor.　Additionally,　benefited　from　the　enhanced　phonon　scattering　by　TiO2　nanoparticles,　a　significantly　decreased　lattice　thermal　conductivity　of　∼0.20　W　m−1　K−1　and　a　high　zT　of　∼0.97　at　390　K　are　obtained　in　the　Ag2Se-based　nanocomposites.　This　work　demonstrates　that　such　cell-membrane-mimic　grain　boundary　engineering　strategy　may　shed　light　on　developing　high-performance　thermoelectric　materials.　©　2023