The interface of Ti-6Al-4V casting and ZrO2 mold with silica binder was investigated by using electron probe microanalyses (EPMA), X-ray diffraction (XRD), and analytical transmission electron microscope (TEM). The interfacial reactions were proceeded by the penetration of liquid titanium through open pores near the mold surface. The metal side consisted of an α-phase layer on the top of the typical α+β two-phase substrate. In the ceramic side, zirconia was reduced by titanium to form oxygen-deficient zirconia ZrO2-x and evolved a gaseous phase (presumably oxygen). The SiO2 binder, dissolved in the ZrO2 mold, could react with titanium to form Ti5Si3 in the metal side. Meanwhile, titanium could transform to titanium suboxides TiyO (y≥2) and the lower phase boundary of cubic ZrO2-x was shifted to ZrO1.76. Some amount of the stabilizer CaO, dissolved in Ti along with ZrO2, could react with Ti(O) to form Ca3Ti2O7 and CaAl4O7 in the reaction zone.