Human Transferrin (HTr) imprinted composite cryogel (HTr-MIPCC) discs were synthesized with distinctive structure and increased adsorption capacity and specificity for HTr by combining the advantages of the surface imprinting technique. HEMA-based cryogel was embedded with HTr-surface imprinted particles. Thanks to the imprinted particles embedding, both the higher surface area and specific recognition are provided. The structure of the HTr-MIPCC was characterized by FTIR Spectrometer, SEM, swelling studies, flow dynamics, and surface area measurements. The addition of surface imprinted particles into the cryogel disc has resulted in an increased surface area, enhancing the capacity of composite cryogel for HTr adsorption up to 10.96 mg/g and gel fractionation yields reached up to 83%. Selectivity studies were carried out against HIgG and HSA as competitors. The HTr-MIPCC discs were packaged into an FPLC column for selective depletion of HTr. It was calculated that the HTr-MIPCC is 1.071 and 1.062 times selective for HTr than HSA and HIgG, respectively. According to FPLC studies HTr-MIPCC can be considered as an excellent alternative for affinity matrixes used for the detection and selective recognition of HTr directly from human serum. HTr-MIPCC discs can be used several times without any noteworthy reduction in the adsorption capacity of HTr.