In this paper, the effect of using different nanofluid as a coolant fluid on the thermal performance of Pillow plate heat exchanger (PPHE) is investigated. The objective of present study is using a new heat transfer enhancement method in PPHE by utilizing nanofluid instead of pure fluid as a heat transfer medium. Accordingly, heat transfer and pressure drop of three water-based nanofluids including Al2O3, CuO and TiO2 are studied by performing three-dimensional numerical simulations by the commercial CFD software. The fluid flow is turbulence, and the analysis is done at different Reynolds number (1000-8000). The results indicate that by increasing the nanoparticle volume concentration in the range of 2-5%, the heat transfer coefficient is improved significantly at low Reynolds number. In order to investigate the heat transfer and pressure drop of the proposed system simultaneously, the performance coefficient parameter is defined. Results showed that the heat exchanger performance is developed significantly at low Re number. On the other hand, the performance of different nanofluids is compared at two volume concentration. The Al2O3-water with phi = 2% at all Reynolds numbers and the TiO2-water with phi = 5% at higher Reynolds numbers have better performance among other nanofluids. (C) 2019 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.