A thermodynamics model was built to simulate and analyze the Stribeck curve of a lubrication system, focusing on the competition between the hydrodynamic effect of the lubricant and the lubricant–substrate interaction effect. For the first time, an entropy production model for a lubrication system was introduced by combining with interfacial disjoining pressure function and interfacial free energy. It reveals that as the film thickness of the lubricant decrease to nanometers, the friction force resulted from interfacial interaction becomes significant and dominant. Meanwhile, the Stribeck curve of the lubrication system presents transition lubrication regime with minimum friction coefficients, namely, valley zone. The Stribeck curve based on the thermodynamic model was simulated and experimentally confirmed by friction tests on silicon wafer substrates modified with different free energies. Test results revealed that a stronger interfacial interaction may cause a smaller friction coefficient within the valley zone on the Stribeck curve, and the corresponding transition regime could be tailored by modifying the interfacial interaction. The proposed thermodynamic model is inclusive and reasonable to reveal the multiscale and multidiscipline effects involved in the lubrication and friction system.