2,4-Dichlorophenol (2,4-DCP) is one of the seriously toxic chlorophenol compounds found in agricultural environments, in water disinfected by chlorine, and in outgoing effluents from the pulp and paper industries and paper manufacturing factories. This research studied the feasibility of using MgO nanoparticles (MgO-NPs) as a catalyst in the ozonation process for removing 2,4-DCP from aqueous environments under laboratory conditions. This study was conducted using a laboratory-scale semi-continuous reactor. It studied the effects of critical variables such as solution pH, ozonation time, dose of MgO-NPs and initial 2,4-DCP concentration. A statistical model of response surface model (RSM) was designed and utilized to obtain the optimum experimental conditions. Analysis of the data showed that initial concentration of 2,4-DCP and dose of MgO-NPs had the maximum effect on the response variable (percentage degradation of 2,4-DCP). Moreover, based on analysis of variance on the model, the optimum removal conditions were reaction time of 50 min, pH > 7, initial 2,4-DCP concentration of less than 50 mg/L, and an MgO-NPs dose of 0.3 mg/L. Under these optimum conditions, a removal efficiency of 99.99% was achieved. In addition, results indicated that catalytic ozonation in the presence of MgO-NPs was very efficient at removing 2,4-DCP from aqueous environments.