In this study, a central composite design (CCD) was applied to evaluate the interactive effects of adsorption variables and to optimize the adsorption process of Ce(III) ions from aqueous solutions onto modified mesoporous silica SBA-15 with N-(2-hydroxyethyl) salicylaldimine (HESI-SBA-15). HESI as a selective and sensitive Shciff base after being immobilized on SBA-15 showed good and repeatable results for the removal of Ce(III) ions. The effect of pH, adsorbent mass, shaking time, and initial concentration of cerium ions was studied by a batch method with inductively coupled plasma/optical emission spectrometry (ICP-OES). The optimal condition was obtained as pH 6; amount of adsorbent, 0.07 g; contact time, 80 min; and concentration of Ce(III) ions, 30 mg L−1. Under the optimal conditions, adsorption was studied in real water samples (99.63% in tap water, 98.20% in river water, and 98.30% in well water), wherein repeatability (relative standard deviation (RSD) 0.006–0.343%) and good recovery (95–97%) were obtained. The adsorption isotherm of cerium was investigated by the Langmuir, Freundlich, and Temkin isotherm models. The Langmuir model was the best model and showed a capacity of 154.86 mg g−1 for Ce(III) ions. The adsorption kinetics was tested with pseudo-first-order and pseudo-second-order models and the results showed that the kinetics of the adsorption process was fitted by the pseudo-second-order model.