Numerical simulating of gas-solid fluidization is crucial to the development of circulating fluidized beds. Accurate simulation entails a structure-dependent drag model based on the sub-grid scale. In this work, a local cluster-structure-dependent drag model is proposed based on the scale resolution of local grid cells, which are resolved into three subsystems to take the effect of heterogeneous flow structure into consideration. The accurate drag correlation based on direct numerical simulation, instead of the Wen & Yu drag correlation, is coupled with the novel drag model to calculate the drag coefficient when the flow structure turns to be homogeneous. In addition, the effect of local solid concentration gradient on the interphase drag force at low voidage is also considered. Then the novel drag model is solved by a genetic algorithm and the obtained drag coefficient is incorporated into the two-fluid model to simulate the gas-solid flow in circulating fluidized bed risers with Geldart A and B particles to validate its accuracy. The results show that the proposed drag model is feasible to capture the heterogeneous flow structure and provide more accurate prediction of solid fluxes and solid concentrations than Gidaspow drag model. In addition, taking the effect of solid concentration gradient into consideration improves the accuracy of prediction, especially in the simulation of CFB risers with Geldart B particles.