Kinetic study was applied for sodium bentonite (Na-B) and hexadecylpyridinium bentonite (HDP-B) under different amounts, namely 50% (50HDP-B), 100% (100HDP-B), and 200% (200HDP-B) with respect to cation exchange capacity (CEC). Pseudo first-order and pseudo second-order kinetic models were performed to optimize the sorption of Congo red (CR) dye from aqueous solution. The experimental data fit the pseudo second order kinetic model well. The sorption capacity (qe) of CR dye by the organo-bentonites at equilibrium was 36.0 mg g−1 (72.1%) for 50HDP-B, 48.05 mg g−1 (96.1%) for 100HDP-B, and 49.2 mg g−1 (98.4%) for 200HDP-B. These results were considerably higher than that found by Na-B. Response surface methodology with three-variable, three-level Box–Behnken design was applied for 100HDP-B to describe the removal of CR dye. The effects of three variables, namely temperature, adsorbent dosage, and initial dye concentration, were studied. Predicted values of adsorption efficiency were found to be in good agreement with the obtained experimental values (R2 = 0.97). A second-order polynomial model successfully described the effects of independent variables on the CR dye removal. At the optimized condition, the toxic azo dye could be quantitatively removed from aqueous solution. The results of the present study suggest that the organo-bentonite can be used as an efficient sorbent for dye removal from aqueous solution.