With the increasing complexity of seismic exploration objects, numerical simulation methods that can accurately describe topographical surfaces and complex geological structures are very important. In this study, we propose a mesh-free finite-difference method for frequency-domain numerical simulation with topography. The mesh-free nodes method theoretically applies to any surface and geological structure, whereas the finite-difference scheme has the advantages of high calculation efficiency, small memory occupation, and high simulation accuracy. Therefore, the mesh-free finite-difference method ensures high efficiency and is suitable for irregular surfaces. In addition, we introduce the perfectly matched layer (PML) absorbing boundary condition into the mesh-free numerical simulation, and we compare the performance of the simplified PML, the classical PML, and the complex frequency-shifted PML methods in suppressing boundary reflections. Then, the complex frequency-shift PML method, which is more accurate in suppressing boundary reflections under topographical surface conditions, is applied to the comparison of the mesh-free and regular grid numerical simulations. The comparisons reflected in snapshots, seismic records, and seismic wavelets demonstrate the effectiveness of the proposed mesh-free finite-difference method. Finally, the proposed numerical simulation method is applied to the Marmousi model and field data with topography to further demonstrate its effectiveness.