Gastrointestinal (G-I) cancers are one of the most common malignant tumors worldwide. Symptoms relate to the organ affected in the G-I tract are non-specific, making early detection and effective treatment difficult to achieve. Epithelial-mesenchymal transition (EMT), a reversible and dynamical process, can disperse cells in embryos, form mesenchymal cells in injured tissues, and regulate embryonic stem cell differentiation. A variety of signaling molecules and distinct pathways are involved in the initiation and progression of EMT. Recent evidence has established that EMT may endow G-I cancer cells with the capacity to invade surrounding tissues, resist apoptosis, migrate to distant organs, and develop chemoresistance. Targeting these signaling molecules and pathways associated with EMT may provide clinicians with a new approach to the treatment of G-I malignancy.