In this study, the Fenton treatment of Monocrotophos (MCP) was evaluated in terms of oxidation and mineralization efficiency using response surface methodology (RSM). The effects of MCP, Fe2+, H2O2 concentrations and reaction time, and the interactions between these factors on (i) the oxidation efficiency of MCP and (ii) the mineralization of MCP were studied. Hence, the objective of this study was to optimize MCP oxidation and mineralization by the Fenton process (FP) using RSM. The obtained optimum conditions for MCP oxidation and mineralization using FP were 0.022: 0.03: 0.15 MCP/Fe2+/H2O2 and a reaction time of 65 min. MCP was mineralized easily through the Fenton reaction. The MCP oxidation efficiency was 90% and the mineralization efficiency was 66%. The initial MCP concentration was the most significant variable affecting both the oxidation and mineralization efficiency of MCP. Addition of Fe2+ had a more significant effect on the MCP oxidation compared to the MCP mineralization.