The β-cyclodextrin nanosponge (NSCD) was synthesized by microwave irradiation method, using β-cyclodextrin (β-CD) as the monomers and diphenyl carbonate (DPC) as the cross linker. The Box-Behnken design of response surface methodology was used to evaluate the interactive effects of temperature, reaction time and the molar ratio〔n（β-CD）:n (DPC）〕on the yield of NSCD. The optimum reaction conditions were obtained as follows: the reaction time was 87 min; the reaction temperature was 90 ℃; the molar ratio was 1:1.75. Under the optimum reaction conditions, the product yield of 70.71% was obtained. The structure and physicochemical properties of the products are characterized by DSC, PXRD, SEM and BET. As the result, the characteristic peaks of carbonyl appeared at 1760 cm-1 in the FT-IR spectrum compared with that of fresh β-CD, which indicate the successful crosslinking of β-CD and DPC; The results of DSC showed the thermal degradation temperature of the NSCD was about 260 ℃ PXRD results shows that the as-synthesized NSCD obtained from our microwave-assisted method had higher crystallinity than those prepared with conventional heating method, consistent with our SEM results. The BET analysis showed an increase in the specific surface area of product as the molar ratio increase, while the pore size changed in the opposite tendency. The reaction time of the optimized process was nearly four times shorter than the traditional method and the yield was increased by 20%~30%.