So-called center and edge segregation are formed during twin-roll casting, which cannot be effectively eliminated in subsequent rolling and heat treatment, thus significantly diminishing the quality of final product. Numerous studies have been conducted on such segregations so far, unfortunately, without fully considering conservation of mass, momentum, energy and solute throughout the process, as well as synergy of thermodynamics and kinetics for interfacial migration. Accordingly, a two-phase Eulerian-Eulerian volume-averaged model is herein established to predict the segregation upon twin-roll casting for Al–Si alloys, which, for the first time, addresses effects due to the interfacial migration and the solute diffusion on the solute transfer process, and so-called correlation between thermodynamics and kinetics (i.e., thermo-kinetic correlation). On this basis, the model accurately predicts the flow field upon twin-roll casting, where, the increased casting speed leads to the descended kissing point, thus gradually causing the decreased vortex area and the increased cooling rate. Whereas, the increased heat transfer coefficient leads to the ascended kissing point, thus gradually causing the increased vortex area and the decreased cooling rate. In the modeling, the increased thermodynamic driving force for interfacial migration is always accompanied by the decreased kinetic energy barrier, and vice versa. Furthermore, the model also accurately predicts the segregation upon twin-roll casting, where, the thermodynamic driving force increases with the casting speed, thus decreasing the central segregation, whereas, the heat transfer coefficient increases, thus enhancing the generalized stability and in turn, effectively suppressing the edge segregation. By employing a strategy involving high driving force in the early stage and high generalized stability in the late stage, it was determined that the anticipated center and edge segregation could be effectively suppressed.