The forced convective heat transfer (CHT) coefficient of a particular nanofluid, Al2O3 nanoparticles-ethylene glycol (EG) mixture, was investigated experimentally in a double-pipe heat exchanger. The nanofluid Nusselt number for different nanoparticles’ concentrations as well as various operating temperatures was measured to be increased up to 23.7% using 1.0% wt of nanoparticles. The significance of this work as novelty are the 22-screening design was used to investigate the effect of factors and the results emphasized that increasing nanoparticles’ concentration has higher effect on the CHT coefficient enhancement of nanofluid. The comparison of experimental results and semi-empirical correlations’ results was done and it was shown considerable deviations for high operating temperatures and nanoparticles as nanostructure concentrations.