The characteristics of heat transfer and pressure drop in turbulent flow of Al2O3 and CuO/water nanofluid that flowing in a horizontal straight square cross-section duct with obstacle has been studied experimentally and numerically. The experimental work is attempted by using a water and nanoparticles concentration of (φ = 0.5 to 2.0 % vol.) that flows in an aluminium square duct with side dimensions of a = 20 mm and length of L = 1000 mm. The obstacle located at the middle of the duct with different obstacle height to pipe side ratio varied as (h/a = 0.0, 0.25, 0.5 and 0.75). The water entered to the duct with inlet Reynolds number of turbulent flow of 3500, 4300, 5200 and 6800. Constant heat flux of 6500 W/m2 is applied upon the external walls of the duct. The numerical finite volume method with appropriate boundary conditions used with ANSYS-Fluent v.16.2 was employed to simulate the temperatures and velocity of the nanofluids. The experimental and numerical results showed that the average Nusselt number increases with increasing the obstacle height ratio and with using nanofluids as compared with pure water. Moreover, the Nusselt number increases with increasing the nanoparticles concentrations in the nanofluids. In addition, the results indicated that increasing in the obstacle height ratio and increasing the nanoparticles, concentration leads to increasing the friction factor and pressure drop. Finally, the numerical results give good indication to the presence of the recirculation cell zone behind the obstacle.