We studied the optimization of hexavalent chromium (Cr(VI)) removal from aqueous solution using the synthesized zero-valent iron nanoparticles stabilized with sepiolite clay (S-ZVIN), under various parameters such as reaction time (min), initial solution pH and concentration of S-ZVIN (g·L^(-1)) using response surface methodology (RSM). The kinetic study of Cr(VI) was conducted using three types of the most commonly used kinetic models including pseudo zero-order, pseudo first-order, and pseudo second-order models. The rate of reduction reaction showed the best fit with the pseudo first-order kinetic model. The process optimization results revealed a high agreement between the experimental and the predicted data (R2=0.945, Adj-R2=0.890). The results of statistical analyses showed that reaction time was the most impressive factor influencing the efficiency of removal process. The optimum conditions for maximum response (98.15%) were achieved at the initial pH of 4.7, S-ZVIN concentration of 1.3 g·L^(-1) and the reaction time of 75 min.