The objective of this study is to assess the hydrothermal performance of a non-Newtonian hybrid nanofluid with tem-perature-dependent thermal conductivity and viscosity compared with a Newtonian hybrid nanofluid with constant ther-mophysical properties. A counter-current double-pipe mini-channel heat exchanger is studied to analyze the effects of thehybrid nanofluid. The nanofluid is employed as the coolant in the tube side, while the hot water flows in the annulus side.Two different nanoparticles including tetramethylammonium hydroxide-coated Fe3O4(magnetite) nanoparticles and gumarabic-coated carbon nanotubes are used to prepare the water-based hybrid nanofluid. The results demonstrated that thenon-Newtonian hybrid nanofluid always has a higher heat transfer rate, overall heat transfer coefficient, and effectivenessthan those of the Newtonian hybrid nanofluid, while the opposite is true for the pressure drop, pumping power, andperformance evaluation criterion. Supposing that the Fe3O4-carbon nanotube/water hybrid nanofluid is a Newtonian fluidwith constant thermal conductivity and viscosity, there leads to large error in the computation of pressure drop(1.5–9.71%), pumping power (1.5–9.71%), and performance evaluation criterion (18.24–19.60%), whereas the errors in thecomputation of heat transfer rate, overall heat transfer coefficient, and effectiveness are not considerable (less than 2.91%).