In this investigation, the combined use of twisted tubes and nanofluid (NF) to augment the performance of a double-pipe heat exchanger (DPHE) has been considered numerically. Steady-state laminar flow of the cold non-Newtonian CuO NF and hot water pass inside the tube side and annulus side, respectively. The base fluid is the aqueous solution of 0.5 mass% carboxymethyl cellulose. The effects of the Reynolds number (Re), the volume concentration of nanoparticles (phi) and twist pitch on the performance metrics are examined, and the outcomes are compared with those a plain DPHE. The outcomes showed that the increase in Re has desirable effects such as improved heat transfer and heat exchanger effectiveness, and unpleasant effects such as increased pressure drop and pumping power. Moreover, it was found that except for phi <= 1.5% and Re=500, the NF performs better than the base fluid. In addition, it was reported that the variation pattern of overall hydrothermal performance of NF with twist pitch is ascending-descending. Furthermore, the outcomes illustrated that the overall hydrothermal performance of twisted DPHE is superior to that of the plain DPHE, and its highest value is 2.671, which belongs to case of Re=2000, phi=3% and twist pitch = 4 mm.