Following predictions by first-principles theory of a huge tunnel magnetoresistance (TMR) effect in epitaxial Fe/MgO/Fe magnetic tunnel junctions (MTJs), measured magnetoresistance (MR) ratios of about 200% at room temperature (RT) have been reported in MgO-based epitaxial MTJs. Recently, a MR ratio of about 600% has been reported at RT in MgO-based MTJs prepared by magnetron sputtering, using amorphous CoFeB as the ferromagnetic electrode. These MTJs show great potential for application in spintronic devices. Fully epitaxial MTJs are excellent model systems that enhance our understanding of the spin-dependent tunneling process as the interface is well defined and can be fully characterized. Both theoretical calculations and experimental results clearly indicate that the interfacial structure plays a crucial role in the coherent tunneling across a single crystal MgO barrier, especially in epitaxial MgO-based MTJs grown by molecular beam epitaxy (MBE). Surface X-ray diffraction, Auger electron spectroscopy, X-ray absorption spectra, and X-ray magnetic circular dichroism techniques have been reported previously for interface characterization. However, no consistent viewpoint has been reached on the interfacial structures (such as FeO layer formation at the bottom Fe/MgO interface), and it is still an open issue. In this article, our recent studies on the interface characterization of MgO-based epitaxial MTJs by X-ray photoelectron spectroscopy, high resolution transmission electron microscopy, and spin-dependent tunneling spectroscopy, will be presented.