One of the advantages of numerical simulations over traditional experimental methodologies is that they can synchronize nucleation, growth and coarsening during solidification from the point of view of microstructural analysis. However, the computational cost and accuracy are bottlenecks restricting simulation approaches. Here, two cellular automaton (CA) modules with different grid dimensions are coupled to form a cross-scale model in order to simulate MnS precipitation, accompanied by the matrix growth of dendrites during the solidification of a Fe-C-Mn-S steel, where the matrix growth is computed through the CA module with large grids based on the solute conservation and the undercooling of thermal, constitutional, and curvature, and increments of solid fraction of MnS are solved in combination with the transient thermodynamic equilibrium on the locally re-meshed grids once the MnS precipitation is formed. We utilize the cross-scale mode to illustrate MnS evolution in a solidifying matrix and explain the reason why it coexists in three shapes. Further, we study the effects of the content of elements Mn and S on MnS precipitation based on two continuously cast steel objects, with the factor of concentration product fixed as a constant. A re-precipitation of MnS is observed during the solidification of a system with a high content of Mn and low content of S. Simultaneous computation using cross-scale modeling can effectively save on computational resources, and the simulation results agree well with the experimental cases, which confirm its reliable accuracy.