In an axial granular bed filter (GBF), a new mesoscale simulation approach is obtained by combining the macroscopic calculation models, i.e., the equations of the total pressure drop and dust-removal efficiency into the porous media model and the source term of the conservation equations. After grid-dependent tests and experimental validation, the effects of different conditions, i.e., granular bed height L, superficial gas velocity ug, dust diameter dp, dust concentration cp, granular diameter dg, initial bed voidage ε0, and filtration time t, on the pressure drop and dust-removal efficiency are investigated. The results show that the pressure drop is related to the inertial and viscous resistance terms, which increase with increasing L, ug, cp and t and decreasing ε and dg. The dust-removal efficiency is related to the Reynolds number, effective Stokes number, and equivalent granular diameter ratio. It increases with increasing L, ug, dp and t (small values), and decreasing cp, ε, and dg. Moreover, the influence of different conditions coincides well with dust-removal efficiency in relevant studies, which further demonstrates the accuracy of the mesoscale simulation approach. With the application of this method, the flow field can also be obtained easily and quickly, which is expected to provide a reference for the simulation study of GBF.