6Li　and　7Li　are　strategic　resources.　Because　Li+　ions　have　no　outermost　electrons　and　the　radii　of　6Li　and　7Li　differ　by　only　one　neutron,　the　separation　of　the　naturally　stable　isotopes　of　Li,　especially　by　solvent　extraction,　is　recognized　as　a　difficult　problem　worldwide.　Therefore,　in　this　paper,　an　advanced　β-diketone-driven　deep　eutectic　solvent　(DES)　extraction　system　containing　2-thenoyltrifluoroacetone　(HTTA)　and　tri-n-octyl　phosphine　oxide　(TOPO)　is　introduced　to　the　extraction　and　separation　of　6Li+　and　7Li+　ions.　Compared　with　those　of　reported　HTTA　extraction　systems　and　crown　ether　extraction　systems,　the　separation　coefficient　((Formula　presented.))　of　the　β-diketone-driven　DES　extraction　system　can　reach　the　best　value　of　1.068,　which　is　now　the　highest　known　β-value　reported　in　the　extraction　system.　From　the　intramolecular　hydrogen　bond　of　HTTA　to　the　intermolecular　hydrogen　bond　of　DES,　the　bond　energy　increases　by　47.8%.　Because　the　active　site　of　the　proton　in　DES　provides　a　higher　energy　barrier　for　the　separation　of　7Li,　the　(Formula　presented.)　is　significantly　increased.　The　extractions　were　characterized　by　spectrum,　using　1H　nuclear　magnetic　resonance　(NMR)　spectroscopy,　Fourier-transform　infrared　(FT-IR)　spectroscopy,　and　X-ray　photoelectron　spectroscopy　(XPS).　The　mechanism　was　determined　on　the　basis　of　the　reaction　kinetics　and　density　functional　theory　(DFT).　The　DES　extractant　shows　excellent　cycle　performance　with　regard　to　stripping　and　reusability.　In　conclusion,　the　highly　efficient,　economical,　and　stable　β-diketone-driven　DES　extraction　system　can　be　used　for　the　separation　of　naturally　stable　Li　isotopes,　which　provides　good　industrial　application　prospects.　©　2023　by　the　authors.