In this research, polyvinyl alcohol (PVA) was chemically cross-linked using epichlorohydrin (ECH). The nanocomposite hydrogels containing copper oxide nanoparticles (CuONPs) were synthesized through immersion of polyvinyl alcohol hydrogel in copper sulfate solution with different concentrations. The produced Cu2+ ions from copper sulfate were bound to hydroxyl groups via metal complexation. With the addition of NaOH solution, Cu2+ ions were converted to copper oxide nanoparticles. The morphology, surface investigation and identification of nanoparticles in polymer matrix were characterized using Fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscopy. Swelling properties of the prepared nanocomposite hydrogels were investigated with various solutions such as the urea, urine, d-glucose, salt solutions (CaCl2 and NaCl) and buffers (pH 1.2 and 7.4). Copper oxide nanoparticles led to an increase in swelling capacity of nanocomposite hydrogels. Indeed, loading and release behaviors of ibuprofen on nanocomposite hydrogels were studied. [GRAPHICS] .