An approach - relaying on application of nanofluid as a working fluid, to improve performance of the two-phase thermosyphon heat exchanger (TPTHEx) has been proposed. The prototype heat exchanger consists of two horizontal cylindrical vessels connected by two risers and a downcomer. Tube bundles placed in the lower and upper cylinders work as an evaporator and a condenser, respectively. Distilled water and nanofluid water-Al2O3 solution were used as working fluids. Nanoparticles were tested at the concentration of 0.01% and 0.1% by weight. A modified Peclet equation and Wilson method were used to estimate the overall heat transfer coefficient of the tested TPTHEx. The obtained results indicate better performance of the TPTHEx with nanofluids as working fluid compared to distilled water, independent of nanoparticle concentration tested. However, increase in nanoparticle concentration results in overall heat transfer coefficient decrease of the TPTHEx examined. It has been observed that, independent of nanoparticle concentration tested, decrease in operating pressure results in evaporation heat transfer coefficient increase.