The mechanism of thermal resistance between graphene layers and nanofluids is essentially important to the performance and reliability of the graphene microchannels. In this paper, the interfacial thermal resistance of the graphenewater, graphene-ethanol, and graphene-ethylene glycol systems are systematically investigated using non-equilibrium molecular dynamics simulations (NEMD). The results showed that the interfacial thermal resistance of the three structures showed different trends as the temperature increased. The interfacial thermal resistance of the graphene-water, the graphene-ethanol, and the graphene-glycol system achieve a minimum value at 285 K, 165 K, and 335 K, respectively. The effects of graphene width on graphene-water interfacial thermal resistance are greater than that of graphene-ethanol and graphene-ethylene glycol systems, however, the thickness of the liquid cluster has greater effect on the interfacial thermal resistance for the graphene-ethanol and graphene-ethylene glycol interfaces than that of graphene-water system. The near-wall density analysis and phonon density of states analysis are calculated to explain the validity of our NEMD simulation results. Our study is helpful for improving the efficiency of the graphene microchannels.