Abstract: Mitochondrial DNA (mt-DNA) is an important carrier of extranuclear genetic information. Recent research results show that mt-DNA is closely related to the occurrence and metastasis of various malignant tumors, and can be used for early diagnosis and targeted therapy of cancer. Therefore, further research on the mechanism of mt-DNA in digestive system malignant tumors has important clinical significance for screening and identifying tumor molecular markers for anti-tumor drug targets, cancer diagnosis and prognosis analysis. This article reviews the research progress on the potential relationship, clinical application and therapeutic targets of mt-DNA and digestive system malignancies.