High-efficiency　adsorption　of　aromatic　sulfur-containing　compounds　from　liquid　hydrocarbon　fuels　over　metal-organic　frameworks　(MOFs)　is　challenging　because　of　inert　metal　sites.　A　new　method,　the　Ce-enhanced　modulation　of　MOFs’　microenvironment,　is　proposed　to　modulate　the　–COO···Cu(II)–　coordination　microenvironment　of　Hong　Kong　University　of　Science　and　Technology　(HKUST-1)　using　Ce(III)　as　a　molecular　scalpel　for　fabricating　abundant　high-efficiency　Cu(I)　and　Cu-coordination-unsaturated　sites　and　improving　the　pore　structures　around　adsorptive　sites.　The　optimal　CH-250　thus　exhibits　adsorptive　capacities　for　20.2,　28.0,　and　58.3 mg S g–1　of　thiophene,　benzo-thiophene,　and　dibenzothiophene,　respectively,　which　are　superior　to　most　reported　MOFs,　zeolites,　and　nanoporous　carbons.　The　constructed　Cu(I)　sites　show　stronger　affinity　for　dibenzothiophene　(−0.86 eV)　than　the　initial　Cu(II)　(−0.74 eV)　for　out-of-plane　adsorption.　Further,　they　are　far　stronger　in-plane　adsorption　interactions　in　DBT/CH-250　(−0.90 eV)　than　those　in　DBT/HKUST-1　(−0.37 eV).　Thus,　molecular　engineering　for　modulating　the　coordination　microenvironment　of　MOFs　shows　great　potential　for　adsorption　desulfurization.　©　2023　Wiley-VCH　GmbH.