Herein, a facile, water-compatible, and one-pot synthesis of a core–shell polysilicate molecularly imprinted polymer (SiO2MIP) on polyvinylpyrrolidone capped gold nanoparticles (AuNPs@PVP) through the condensation polymerization of vinyltrimethoxysilane (VTMS) as a functional monomer, tetraethoxysilane (TEOS) as a cross-linker, and uric acid (UA) as a template has been reported. The response surface methodology based on central composite design (RSM−CCD) was used to optimize the conditions of the reaction. The characteristics of the resulting composite (AuNPs@PVP@SiO2MIP) produced under the optimized conditions were evaluated using UV–vis spectroscopy, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), cyclic voltammetry (CV), and water contact angle measurement. Next, the as-synthesized AuNPs@PVP@SiO2MIP served as a novel electrochemical platform for the detection and determination of UA in a urine sample. Differential pulse voltammetry (DPV) was used to construct the calibration curve that showed two linear concentration ranges. In addition, the limits of detection (LOD) and quantification (LOQ) of the method were obtained to be 4 × 10−7 and 1 × 10−6 M, respectively. Also, the repeatability and reproducibility of the sensor (RSD%) were achieved to be 7% (n = 8) and 3% (n = 5), respectively. At last, the proposed sensor was successfully applied for the measurement of UA in a urine sample.