Circular RNAs (circRNAs) are a series of special closed circular RNA molecules with stability and conservatism. In recent years, advances in high-throughput RNA sequencing technology have led to explosive discovery of circRNAs in different types of species and cells. Moreover, circRNAs can accomplish a remarkable multitude of biological functions, such as regulating transcription or splicing, serving as miRNA sponges, interacting with RNA-binding proteins, and translating proteins. Meanwhile, circRNAs involve in the biogenesis and development of many diseases, including cardiovascular disorders, nervous system disorders, cancers, etc. Herein, we discuss the latest research progress of circRNA, as well as their diagnostic and prognostic significance in digestive system cancers. In addition, this paper highlights that circRNAs might serve as potential therapeutic targets for novel drugs by taking digestive system cancer as an illustrative example.