Hot-core heavy reduction rolling (HHR2) is an innovative technology, where a two-high rolling mill is installed after the solidification end of a strand, which can significantly eliminate the core defects of the slab. The mill exhibits a heavy reduction ratio, which promotes the dynamic recrystallization (DRX) of the slab. This study aims to optimize the parameters of the HHR2 process considering the effect of DRX on microstructure homogeneity. The secondary development of commercial software DEFORM-3D is conducted to calculate the deformation and DRX behavior of HHR2 for different reduction ratios. The parameters of DRX volume fraction and DRX grain size are compared, and finer DRX grains are obtained when the greater reduction ratios are conducted in HHR2. Then, corresponding to the deformation conditions in the HHR2, the thermal–mechanical simulations are conducted on the Gleeble3800 to obtain the average grain sizes before and after this process. When the reduction amount increases from 20 mm to 50 mm, the difference of average grain size between the core and the surface reduces by 52%. In other words, appropriately enhancing the reduction ratio is helpful to reduce the average austenite grain and promote the microstructure uniformity of the slab. These results provide some valuable information on the design of deformation parameters for HHR2.