Tetragonal-phase Pr2CuO4 nanosheets with a thickness of about 60 nm were synthesized using the coordination compound methods (CCMs), then used as highly efficient selective adsorbent towards malachite green (MG) in aqueous solutions. The Pr2CuO4 samples were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), UV-Vis diffuse reflectance spectrum (DRS), and standard Brunauer–Emmett–Teller (BET) methods. The maximum adsorption capacity (Qm) of as-prepared samples was determined by adsorption isotherms with different adsorbent doses (m) of 0.03–0.07 g at 298, 318, and 338 K based on the Langmuir model. When m < 0.03 g or > 0.07 g, effects of systemic mass loss and particle aggregation were discussed on the data deviation from the Langmuir model at 298 K. Based on the hydrogen bond and coordination bond, a possible mechanism of selective adsorption of MG by Pr2CuO4 is proposed, which was further verified by the adsorption experiments of CuO and Pr2O3 towards MG and competing-ion experiments. Finally, the theoretic studies were performed at DFT level to reveal the possible adsorption process.