Abstract: HOTTIP RNA is a type of long non-coding RNA, which is transcribed from the HOXA gene at its distal tip and coordinates the activation of 5'HOXA genes. Particularly, it regulates the expression of the neighboring HOXA 13 gene. Recently, emerging lines of evidence have suggested that increased expression of HOTTIP is observed in digestive system carcinomas, including esophageal cancer, gastric cancer, hepatocellular carcinomas, pancreatic cancer, and colorectal cancer, and is closely associated with the initiation and progression of cancer, and affects the survival and prognosis of cancer patients. Therefore, it is expected to be a diagnosis index marker, prognosis indicator, and a new therapeutic target for the relevant tumors. Here, we focus on the discovery of lncRNA HOTTIP, its mechanism, and the latest developments in the research on HOTTIP in digestive system carcinomas.