<p>tRNA-derived small RNAs (tsRNAs) is a type of non-coding RNA that is present in large quantities in humans and exhibits high stability. It plays a crucial role in various physiological processes and diseases. In recent years, research on tsRNAs in tumors has expanded significantly, revealing its regulatory effects in non-neoplastic diseases as well. Additionally, tsRNAs has been extensively studied in the context of digestive system diseases, encompassing both digestive system tumors and non-tumor conditions. It is believed to influence the biological characteristics of diseases as well as clinical pathological features. Given its potential, tsRNAs is anticipated to have broad applications in disease diagnosis and prognosis prediction, and it is expected to emerge as a new class of biomarkers. Nevertheless, numerous issues remain that require in-depth discussion. This article presents an overview of the characteristics and roles of tsRNAs in digestive system diseases, aiming to provide a comprehensive perspective and to inspire new ideas for the diagnosis and treatment of these conditions.</p>