The phenolic compounds are known as priority pollutants, even in low concentrations, as a result of their toxicity and non-biodegradability. For this reason, strict standards have been established for them. In addition, chlorophenols are placed in the 38th to 43th in highest priority order of toxic pollutants. As a consequence, contaminated water or wastewaters with phenolic compounds have to be treated before discharging into the receiving water. In this study, Response Surface Methodology (RSM) has been used in order to optimize the effect of main operational variables responsible for the higher 4-chlorophenol removal by Activated Carbon-Supported Nanoscale Zero Valent Iron (AC/NZVI). A Box-Behnken factorial Design (BBD) with three levels was applied to optimize the initial concentration, time, pH, and adsorbent dose. The characterization of adsorbents was conducted by using SEM-EDS and XRD analyses. Furthermore, the adsorption isotherm and kinetics of 4-chlorophenol on AC and AC/NZVI under various conditions were studied. The model anticipated 100% removal efficiency for AC/NZVI at the optimum concentration (5.48 mg 4-chlorophenol/L), pH (5.44), contact time (44.7 min) and dose (0.65g/L). Analysis of the response surface quadratic model signified that the experiments are accurate and the model is highly significant. Moreover, the synthetic adsorbent is highly efficient in removing of 4-chlorophenol.