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The interaction of MgO–MgAl2O4-based and MgO–Cr2O3-based refractories with X70 molten steel was studied by immersion experiments at 1560 °C. The effects of immersion time (30 and 60 min) on the contents of total oxygen (TO), Al, Nb, Si, Mn, and Cr as well as the composition, number density, and size distribution of inclusions in the molten steel were investigated. The influence of the penetration and erosion degree of the molten steel to the refractory on the steel–refractory interface layer was analyzed. The results show that, at 1560 °C, the MgO–MgAl2O4-based refractory can better control the contents of TO and the composition of molten steel compared with the MgO–Cr2O3-based refractory. The TO content is only 16 × 10−4wt.% in the molten steel after reacted with the MgO–MgAl2O4-based refractory at the end point of refining, accounting for 11.5% of that reacted with the MgO–Cr2O3-based refractory (139 × 10−4wt.%). The number density of inclusions is only 14 mm−2, and the average size of inclusions is only 1.31 μm, with the largest proportion of inclusions in 1–2 μm (70%). The Al2O3–MnS–CaO complex inclusions in the original steel changed to complex inclusions dominated by Cr–Nb–Mn–S–O and MgO·Al2O3, corresponding to the MgO–Cr2O3-based and MgO–MgAl2O4-based refractories, respectively. The MgO·Al2O3layer was formed at the reaction interface between MgO–MgAl2O4-based refractory and molten steel, which is helpful to restrict the erosion of refractories and the pollution of molten steel. The damage mechanism of the MgO–Cr2O3-based refractory is mainly permeation and chemical reaction, while the damage of the MgO–MgAl2O4-based refractory is mainly scouring erosion.