Ducts with a square cross-section are widely used in many industrial applications because of their high compactness, easy forming, and low pressure drop. But the thermal performance of a duct will be reduced when the circular cross-sectional shape is not used. In this study, the convective heat transfer for a CuO/water nanofluid through a square cross-section duct in the turbulent flow regime has been investigated. The Nusselt number of nanofluids for different nanoparticle concentrations, as well as various Peclet numbers, was obtained. The results show considerable enhancement in the heat transfer coefficient and Nusselt number by increasing the nanoparticle concentrations as well as the Peclet number.