4-Chlorophenol (4-CP) is a hazardous and toxic chemical that enters into water bodies mainly through industrial effluents. The present study investigated the effect of under pressure dissolved oxygen on 4-CP degradation in the presence of nanoscale zero-valent iron (nZVI) and sodium persulfate. The impact of oxygen pressure, as a qualitative variable at three levels (1, 1.5 and 2 atm), along with five quantitative variables, including persulfate concentration (0-2mM), nZVI dosage (0-1 g/L), pH (3-11), reaction time (5-90min) and 4-CP concentration (50-500mg/L) on the 4-CP elimination from aqueous solutions, was examined using response surface methodology. There was a direct relationship between the dissolved oxygen under pressure and the 4-CP removal efficiency. Also, the gained R² and adjusted R² for three developed models of 1, 1.5 and 2 atm oxygen pressure were 0.971 and 0.9569, 0.9689 and 0.9538, and 0.9642 and 0.9468, respectively. The best removal process conditions for pH 4.2, 1.6mM persulfate, 64.79 min reaction time, 97.89mg/L initial 4-CP and 1 g/L nZVI dosage. The results indicated that dissolved oxygen under pressure-nZVI-persulfate could be considered a promising process for elimination of organic compounds from aqueous solutions.