Silent information regulator 3(SIRT3), a member of the silent information regulator family, primarily regulates mitochondrial metabolism, and plays a critical role in age-related diseases, neurodegenerative disorders, as well as cardiac, hepatic, renal, and metabolic diseases. Notably, in cancer, SIRT3 exhibits both tumor-suppressive and tumor-promoting functions, making it a promising therapeutic target. This review systematically summarizes the complex molecular mechanisms of SIRT3 in tumorigenesis and its roles in various malignant tumors, including colorectal cancer, lung cancer, hepatocellular carcinoma, ovarian cancer, gallbladder cancer,cholangiocarcinoma,and pancreatic cancer. Elucidating the mechanisms of SIRT3 not only contributes to revealing the molecular basis of tumorigenesis, but also holds promise for promoting the development of novel antitumor agents targeting SIRT3, thereby providing new directions for clinical cancer therapy.