A nickel monosubstituted polyoxometalate (POM)/polyaniline organic–inorganic hybrid SiW 11 Ni/PANI was synthesized using the liquid-phase method at room temperature to achieve the solidification of water-soluble POMs. The SiW 11 Ni/PANI hybrid was characterized by scanning electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, X-ray diffraction, and zeta potential. On the basis of π–π stacking and affinity interaction between the SiW 11 Ni/PANI hybrid and proteins, the SiW 11 Ni/PANI hybrid showed good adsorption selectivity to hemoglobin (Hb). At pH 7.0, 0.5 mg of SiW 11 Ni/PANI resulted in an adsorption efficiency of 92.4% for 1 mL of 100 μg mL –1 Hb. The adsorption behavior of Hb on the surface of the hybrid fitted with the Langmuir model, and the maximum adsorption capacity was 692 mg g –1 . The adsorbed Hb was eluted by BR (0.04 mol L –1 , pH 9), providing a recovery of 94%. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis assay results indicated that the Hb in human whole blood could selectively be adsorbed by the SiW 11 Ni/PANI hybrid, and the obtained Hb was with high purity. It could expand the application of POMs in life science due to the application of the POM hybrid in protein isolation/purification.