The tunneling electroresistance (TER) ratio is an important device merit of ferroelectric tunnel junction (FTJ) and multiferroic tunnel junction (MFTJ) devices. Here, through first-principles calculations, we propose an efficient way to achieve a sizable TER effect through the interface engineering in both SrRuO3/PbTiO3/FeO/Fe and SrRuO3/PbTiO3/CoO/Co MFTJs. It is found that the interfacial FeO or CoO layer can significantly modify the band alignment between PbTiO3 barrier and electrodes through its large depolarization field, causing the insulating–metallic transition of PbTiO3 barrier upon polarization reversal. As a result, the tunneling resistance changes significantly, leading to a giant TER effect of 105%. Our results suggest a practical way to enhance the TER effect in MFTJs.