This paper presents a numerical analysis for Cu-water nanofluid flow through a circular duct inserted with cross-cut twisted tape with alternate axis (CCTA). Three dimensional (RNG) k − ϵ turbulence model is applied to simulate this problem. All simulations are performed for plain tube and nine different CCTA geometries in the range of width ratio (b/w) from 0.7 to 0.9, length ratio (s/w) from 2 to 2.5, Reynolds numbers in the range of 5000 to 15,000 and volume fraction of nanoparticles from 0 to 1.5%. The calculated results indicate that the swirl flow created by CCTA is transferred from the tube core to the near wall regions. This results in higher fluid mixing, which enhances heat transfer and friction factor near the tube wall. The results show that the heat transfer coefficient increases up to 23.20% with increasing the nanoparticle volume fraction from 0% to 1.5%. Finally, it is shown that the thermal performance increases by increasing the volume fraction of nanoparticles inside the duct.