A simplified two-fluid model (STFM) combined with energy-minimization multi-scale (EMMS) drag was proposed for accurate and fast simulation of gas-solid flows. In the proposed approach, the solid phase viscosity is neglected, the solid phase pressure is calculated with an empirical formulation, and the interphase momentum transfer is modeled with EMMS drag, which takes the effects of meso-scale structures into consideration. Three typical fluidization cases, namely, a 2D circulating fluidized bed, a 3D lab-scale bubbling fluidized bed, and a 3D lab-scale full-loop circulating fluidized bed, were successfully simulated with this approach. The numerical results are compared with those of full two-fluid model (FTFM, i.e., the two-fluid model using the kinetic theory for granular flow to close solid phase stress term), as well as experimental data. Predictions of STFM coupled with EMMS drag are comparable with those of FTFM coupled with EMMS drag, and both agree well with experimental data. However, computational cost of STFM is significantly reduced compared with that of FTFM. It is suggested that drag model has a dominant effect on gas-solid simulation, and the effect of solid phase stress term seems to play a minor role, demonstrating the feasibility and practicality of STFM with EMMS drag for describing the hydrodynamics of heterogeneous gas-solid flows.