At present, the common tool for affinity purification of IgG is immobilized Protein A, which is separated from native cell-wall components of Staphylococcus aureus. It is complicated and costly to prepare natural Protein A. ZZ protein is a synthetic Fc region-binding domain originated from B domain of Protein A. In the present study, recombinant ZZ protein with a hexahistidine tag at the N-terminus was expressed in BL21 (DE3) under the control of T7 promoter. The protein was purified through one-step Ni2+ chelating affinity chromatography at a yield of 50 mg of protein/litre of culture. Then it was covalently coupled with Sepharose 4B with butane-1,4-diol diglycidyl ether. The protein ZZ-Sepharose 4B resin exhibited good performance in affinity purification of IgG, as well as in capturing the protein-interacting complexes in immunoprecipitation experiments. Compared with natural Protein A, the expression and purification of ZZ protein at high yield are very simple and low-cost. At this point, extensive applications of protein ZZ in immunoassays are practicable and to be anticipated.