The interfacial reaction between alumina refractory and CaO-CaF2-SiO2-Al2O3-MgO-MnO slag was observed at 1873K to estimate the stability of the spinel phase using computational thermodynamics under refining conditions of Mn-containing steels. The concentration of MnO formed by the slag-steel reaction in the CaO-CaF2-SiO2-Al2O3-MgO melts generally increased by decreasing the CaO/SiO2 ratio of the initial melts. No intermediate compounds were formed at the refractory-slag interface when the initial CaO/SiO2 ratio was 0.5, whereas CaAl12O19 (CA6) and Mg(Mn)Al2O4 (spinel), identified from TEM analysis using EDS mapping and SAED patterns, were observed at the refractory-slag interface when the CaO/SiO2 ratio was 1.0 or greater. The (at.%Mg)/(at.%Mn) ratio in the spinel solution increased by increasing the CaO/SiO2 ratio, which originated from the fact that MgO activity continuously increased as the CaO/SiO2 ratio increased. From thermodynamic analysis considering the equilibrium constant (K-SP) and activity quotient (Q(SP)) of the spinel formation reaction at the slag-refractory interface and the bulk slag phase, the precipitation-dissolution behavior of the spinel phase was predicted, which exhibited good consistency with the experimental results. Hence, the dissolutive corrosion mechanism of alumina refractory into the CaO-CaF2-SiO2-Al2O3-MgO-MnO slag was proposed.