A eutectic mixture solvent (EMS) system containing 1,4-butylene glycol (1,4-BDO), choline chloride (ChCl), and sucrose was proposed for the conversion of sucrose to 5-hydroxymethylfurfural (HMF) with mesoporous hollow silica−alumina nanosphere (SAN) catalyst. The EMS system can form a solid at room temperature after the reaction since the adequate composite proportion of EMS components is conducive to the separation of the product and the recovery of the solvent system. The reaction mechanism of the EMS−SAN system that catalyzed the conversion of sucrose was detailed by nuclear magnetic resonance, electrospray ionization mass spectra experiments, and density functional theory calculation. The complete conversion of sucrose benefits from the hydrogen-bond interaction between 1,4-BDO, ChCl, and sucrose system as well as the synergistic effect of Bronsted and Lewis acid sites on SAN catalyst. The hydrogen-bond interaction energy in the sucrose−1,4-BDO−ChCl system was −55.28 kcal mol −1 , implying that the higher hydrogen bond energy between sucrose and EMS components improved the HMF formation.