Experiments on 45 steel with high-velocity impact were carried out in order to study the target resistance. Then the influence of impact velocity and target parameters on the penetration resistance was analyzed by the calculation model. Also, the DOP (depth of penetration) of different projectiles penetrating 45 steel targets were studied based on the hydrodynamic penetration model. It was shown that the experimental results of penetration resistance based on the material dynamic hardness test method agrees well with the theoretical calculation results of hydrodynamic penetration model. Simultaneously, with the increase of impact velocity, the target resistance reduces from 5.13 GPa to 3.7 GPa. Also, the target resistance shows linear trend increase with the increase of the dynamic yield strength of targets. The DOP calculated by the hydrodynamic penetration model agrees well with the corresponding experimental data. All of these proved that the method to obtain dynamic resistance is feasible, thus can provide a reference for hypervelocity penetration dynamics research.