•Assessment of the thermal performance of microchannel heat sink with nanofluid is studied.•The maximum suppression of the thermal resistance attained by employing the nanofluid is about 12.61%.•The maximum enhancement of the nanofluid for the heat transfer coefficient is up to 14.43%. By increasing demands for high thermal performance and energy efficiency, attentions to microchannel heat sinks (MCHSs) as the suitable method for heat flux dissipation from thermal systems have increased significantly. Microchannel heat sinks can be widely employed in electronic devices for higher heat removal rate and to provide best performance and durability for electronic systems. The critical issue associated with MCHSs is their ability for integration of effective thermal performance. In this work, on the assessment of the thermal performance of microchannel heat sink with nanofluid is experimentally examined. The heat removal performance of the pure water and nanofluid through the MCHS is studied. Different important parameters, such as dimensionless wall temperature, pressure drop, mean convection heat transfer coefficient, thermal resistance, and uniformity index, are investigated. The results indicated that the maximum suppression value of the thermal resistance attained by employing the nanofluid is 12.61%. The uniformity index of the heating surface is increased as the Re number increases. More suppression in the wall temperature can be observed as the volume concentration of nanoparticles is increased. By increasing the total flow rate and using the nanofluid, the hot spots on the heating surface are suppressed. Finally, the maximum gain value of the nanofluid for the mean convection heat transfer coefficient is up to 14.43%.