Abstract: Metformin is a first line therapeutic agent that has been used to treat type Ⅱ diabetes mellitus, it also has been reported to be a potential anticancer drug which have cancer prevention effects or synergistic effects with chemotherapeutics against various cancers including breast cancer, lung cancer, liver cancer, endometrial cancer, colorectal cancer, and so on. In recent years, numerous studies tend to combine metformin with chemotherapeutics to achieve a significant anti-tumor effect with lower systemic toxicity and to improve survival and prognosis of the patients. In this review, the synergistic anticancer mechanisms of metformin combined with chemotherapeutics and its application in clinical research were summarized.