Abstract: The occurrence and development of tumors is a biological process that is extremely complex. In depth research gradually revealed that mitochondria play an important role in the metabolism of tumor cells. The types of mitochondrial DNA (mtDNA) mutations identified contain point mutations, deletions, insertions, and copy-number variations. These mutations may be involved in the proliferation, growth, invasion, and metastasis of tumor cells. In this study, mtDNA mutations, copy-number changes, correlation of mtDNA with nuclear DNA, and the progress gained in the development of the relationship between mtDNA mutations and tumorigenesis are detailed. This review aims to provide additional references to improve the understanding of the relationship between mtDNA mutations and tumor progression.