Room temperature ionic liquid (RTIL) 1-butyl-3-methylimidazolium hexafluorophosphate (BMIM·PF6) has been successfully immobilized on mesocellular siliceous foams (MSFs) by using a specific annealing method. Nitrogen adsorption/desorption isotherms and scanning electron microscopy (SEM) images reveal that most pores of MSFs are filled with the RTIL and the outer surfaces of MSFs are covered with the RTIL. When hemoglobin (Hb) is immobilized with the resulting hybrid material on a glassy carbon electrode (GCE), a pair of well-defined and quasi-reversible voltammetric peaks for Hb Fe(III)/Fe(II) is obtained. Its formal potential is −0.330V (vs. saturated calomel electrode) in pH 7.0 phosphate buffer solution (PBS). The peak currents are much larger than those of Hb immobilized with MSFs or BMIM·PF6–MSFs mixture. This indicates that the hybrid material has stronger promotion to the direct electron transfer of Hb, which is related to the effective immobilization of BMIM·PF6 on MSFs. The electron-transfer rate constant (k s) is estimated to be 1.91s−1. The immobilized Hb retains its native conformation and shows high electrocatalysis to the reduction of H2O2. Under the optimized experimental conditions, the catalytic current is linear to the concentration of H2O2 from 0.2 to 28μM, and the detection limit is 8×10−8 M (S/N=3). The linear range is wider than those for Hb immobilized with MSFs or BMIM·PF6–MSFs mixture. Thus, the MSFs supported RTILs hybrid material is an ideal matrix for protein immobilization and biosensor fabrication.