Abstract: Rab proteins are small GTP-binding proteins belonging to the Ras protein superfamily. To date, more than 70 Rab family members have been identified that are distributed in a wide range of different membrane structures in various cell types. They act as regulators of vesicle transport, protein transport, and membrane targeting and fusion and participate in regulating cell growth and programmed death (apoptosis). A large number of studies have shown that abnormally-regulated Rab proteins affect cell physiology in cancer by disrupting homeostasis in cell membrane transport, key cell signaling pathways, and specialized secretion pathways. The Rab27 subfamily belongs to the Rab protein family and includes Rab27A and Rab27B,which have similar but not identical functions. Rab27A and Rab27B are not only important molecules in regulating vesicular transport but are also closely related to growth, invasion, and metastasis in a variety of tumors and can be used as therapeutic targets and prognostic markers in tumor therapy. Steadily increasing evidence shows that Rab27 plays an indispensable role in the occurrence and development of tumors. This article reviews research progress in investigations of Rab27 in digestive system tumors.