Detection of protein C (PC) in human serum was performed by quartz crystal microbalance (QCM) based on molecular imprinting technique (MIP). The high-resolution and mass-sensitive QCM based sensor was integrated with high sensitivity and selectivity of the MIP technique. The PC microcontact imprinted (PC-mu CIP) nanofilm was prepared on the glass surface. Then, the PC-mu CIP/QCM sensor was prepared with 2-hydroxyethyl methacrylate (HEMA), ethylene glycol dimethacrylate (EGDMA) and N-methacryloyl L-histidine methylester (MAH) as the functional monomer with copper(II) ions. The polymerization was performed under UV light (100W and 365 nm) for 20-25 min under nitrogen atmosphere. The characterization studies of QCM sensor were done by observation using atomic force microscopy (AFM), contact angle measurements, ellipsometry and fourier transform infrared spectroscopy (FTIR). Detection of PC was investigated in a concentration range of 0.1-30 mu g/mL. Selectivity of PC-mu CIP and PC non-imprinted/QCM (PC-non-mu CIP) sensors for PC determination was investigated by using proteins namely hemoglobin (Hb), human serum albumin (HSA) and fibrinogen solutions. QCM sensor was also used for detection of PC molecules in aqueous solutions and human plasma. The detection limit was determined as 0.01 mu g/mL for PC analysis. The PC-mu CIP/QCM sensor was used for five consecutive adsorption-desorption cycles. According to the results, the PC-mu CIP/QCM sensor had obtained high selectivity and sensitivity for detection of PC molecules. (C) 2016 Elsevier B.V. All rights reserved.