In the last 20 years, microRNAs (miRNAs) have become the most promising class of diagnostic and prognostic biomarkers for human cancer. From a therapeutic perspective, advances in the understanding of the molecular role of miRNAs in the pathological processes have significantly influenced the selection of new therapeutic modalities. Moreover, the intrinsic characteristics that confer stability to miRNAs in vitro, allow a longer molecular/structural resistance and activity in vivo. Preclinical models have consistently underlined the feasibility and efficacy of miRNA-based therapies, either alone or in combination with current targeted therapies. The appealing strength of such therapeutic option dwells in miRNAs' ability to concurrently target multiple genes, frequently in the context of a specific network/pathway. This property allows miRNA-based therapy to be extremely efficient in regulating distinct biological processes relevant to normal and pathological cell homeostasis. The purpose of this review is to summarize the role of miRNAs in gastrointestinal carcinogenesis and their potential use as novel biomarkers and therapeutics.