The desulfurization capacity of top slag in the process of pre-desulfurization of hot metal containing vanadium and titanium was researched. The top slag system of CaO-SiO2-MgO-Al2O3-TiO2-VOx that was formed by blast furnace slag and a CaO desulfurization agent reduced the sulfur in hot metal from 0.08 wt.% to 0.02 wt.%. It was found that the resulfurization of the slag happened in the later periods of the desulfurization process. The vanadium–titanium oxides were both acidic in the desulfurization slag. TiO2 and VOx reacted with the basic oxides to form CaTiO3 and MgV2O4 at 1623 K, which reduced free CaO and was not conducive to top slag desulfurization. The results of calculation showed that the top slag desulfurization accounted for 15% of the total desulfurization. Using the ionic and molecule coexistence theory of slag structure, it is shown that the desulfurization efficiency could be enhanced by adjusting both the amount of desulfurization agent and the composition of the blast furnace slag before pre-desulfurization.