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 Al_2O_3–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–ε 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 minimum level 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 Al_2O_3 averagely 17% and TiO_2 10% improve the Nusselt numbers. 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 Al 2 O 3 -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-ε 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 minimum level 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 Al 2 O 3 averagely 17% and TiO 2 10% improve the Nusselt numbers.