Adsorption of U(VI) ions from aqueous solution onto a novel amidoximated modified calcium alginate bead with entrapped functionalized SiO2 nanoparticles, (alginate/SiO2/TMPTMS/PAO), with variation in SiO2 and 3-mercaptopropyltrimethoxysilane (TMPTMS) contents was studied. In order to synthesis of the composite adsorbent, SiO2 nanoparticles were first modified via TMPTMS and then applied to prepare the alginate gel beads. The adsorption capacity of U(VI) ions by alginate/SiO2/TMPTMS/PAO beads at 5 wt % of SiO2 and 30 wt % of TMPTMS (with respect to the alginate weight) was 3.6 times greater than that of the blank one (alginate/PAO). The characterizations of adsorbent were carried out using FTIR, SEM-EDX and BET analyses. The equilibrium and kinetic data were well described by the Langmuir isotherm and Pseudo-second order kinetic models, respectively. The effect of operating variables, including initial pH of solution, initial concentration of U(VI) solution and the dosage of adsorbent on the adsorption capacity of uranium ions were investigated by central composite design (CCD) of response surface methodology (RSM). The effect of presence of copper, cadmium and nickel ions on the adsorption of uranium ions in binary systems was investigated. In this work, for the first time, modified SiO2 nanoparticles with –SH group, have been added to the calcium-alginate gel beads to increase the mechanical, thermal and radiative resistance of alginate as well as to increase the uranium adsorption capacity. The results showed that alginate/SiO2/TMPTMS/PAO composite adsorbent was effective in removal of U(VI) ions from aqueous solutions.