In this paper, response surface methodology (RSM) based on central composite design (CCD) is applied to obtain an optimization design for the fuel rod's diameter and distance cooled by turbulent Al2O3-water nanofluid for a typical pressurized water reactor (PWR). Fuel rods and nanofluid flow between them are simulated 3D using computational fluid dynamics (CFD) by ANSYS-FLUNET package software. The RNG k-epsilon model is used to simulate turbulent nanofluid flow between the rods. The effect of different nanoparticles concentration is also investigated on the Nusselt number from heat transfer efficiency view point. Results reveal that when distance parameter (a) is in the minimumlevel and diameter parameter (r) is in the maximum possible level, cooling the rods will be better due to higher Nusselt number in this situation. Also, using the different nanoparticles on the cooling process confirms that Al2O3 averagely 17% and TiO2 10% improve the Nusselt numbers. (C) 2016 The Chemical Industry and Engineering Society of China, and Chemical Industry Press. All rights reserved.