•quantification of Annexin A3 in biological samples at ng/mL levels;•novel Protein Imprinted Material based on electropolimerization of caffeic acid;•successful use of the sensor on the analysis of Annexin A3 in urine samples;•good sensitivity, selectivity and sensor stability was achieved. The development of fast and reliable methods for protein determination are of great relevance to a diversity of areas from industry to diagnostics. Molecular Imprinted Materials (MIM) has proved to be an interesting methodology for protein analysis however further studies of the effect of the experimental parameters and starting materials in the performance of the MIM are still required. Caffeic acid (CAF) is employed for the first time as a monomer to tailor a synthetic receptor for a protein target. This was done by bulk-electropolymerization, applying a constant potential of +2.0V, for 30s, on a carbon screen-printed electrode, immersed in a solution of protein and CAF prepared in phosphate buffer. Annexin A3 (ANXA3) was selected as protein target due to the fact that this is an emerging biomarker in prostate cancer. The assembly of the protein imprinted material (PIM) was followed by Electrochemical Impedance Spectroscopy (EIS) and Raman Spectroscopy. A non-imprinted material (NIM) was prepared in parallel as control. Square wave voltammetry (SWV) was used to monitor the electrochemical signal of the Fe(CN)63−/Fe(CN)64− redox for the quantification of ANXA3. The optimized PIM-based device showed average detection limits (LOD) of 0.095ng/mL, a linear behavior against log (concentration) between 0.10, and 200ng/mL and good selectivity. The NIM-based device showed random behavior against protein concentration. Finally, the PIM-sensor was successfully applied to the analysis of ANXA3 in spiked urine samples.