Gastrointestinal (GI) cancers, especially including esophageal, gastric and colorectal cancer, are common types of cancer with high morbidity and mortality worldwide. Despite great advances having been made for these cancers, current treatments including surgery, Radiotherapy (RT) and Chemotherapy (CT) are still far from satisfactory as these cancers are usually discovered in advanced stages that are associated with short longevity and poor outcomes. MicroRNAs (miRNAs) are short noncoding strands of RNA that regulate gene expression, affecting proliferation, development, differentiation, apoptosis, metabolism and Epithelial-mesenchymal Transition (EMT). The miR-17-92 cluster was detected as “oncomir-1”, which is involved in the onset and progression of numerous human cancers. This review presents the recent developments in knowledge about miR-17-92 clusters for diagnosing and treating GI cancers based on genetic functions, biological phenotypes, related mechanisms, biomarkers and therapeutic perspectives, which could provide a wider horizon for future use.