In this work, the thermo-sensitive materials N-isopropylacrylamide (NIPAM) and acrylic acid (AA) were crosslinked with carboxymethyl cellulose (CMC) (CMC/P (NIPAM-co-AA)) via a free radical polymerization method for the removal of U(VI) from aqueous solution. The L16 (45) orthogonal experiments were designed for the optimization of the synthesis condition. The chemical structures of the crosslinking hydrogel were confirmed by FTIR spectroscopy. The microstructural analyses were conducted though scanning electron microscopy (SEM) to show the pore structure of the hydrogel. The adsorption performance of the CMC/P (NIPAM-co-AA) hydrogel for the uptake of U(VI) from simulated wastewater was also investigated. The adsorption reached equilibrium within 1 h. Under the reaction of pH = 6 and a temperature of 298 K, an initial concentration of U(VI) of 5 mg·L−1, and 10 mg of the CMC/P(NIPAM-co-AA) hydrogel, the maximum adsorption capacity was 14.69 mg g−1. The kinetics fitted perfectly with the pseudo-second-order model, and the isotherms for the composite hydrogel adsorption of U(VI) was in accordance with the Langmuir model. The chemical modification confirmed that the acylamino group played an important role in uranium adsorption. The desorption and reusability study revealed that the resolution rate was still available at approximately 77.74% after five alternate heating cycles at 20 and 50 °C of adsorption-desorption.