Abstract: Compared with normal individuals, diabetic patients have a much higher risk of suffering from various kinds of cancer, however, the cause or underlying mechanism are not fully understood. It is generally believed that hyperglycemia, hyperinsulinemia and insulin resistance are highly related. Epidemiology study also showed that the application of insulin and sulfonylureas in diabetes therapy has also been associated with cancer incidence and mortality probably due to the increased plasma insulin level and the aggravated insulin resistance. Whereas, metformin could significantly reduce the risk of cancer by improving insulin resistance and decreasing plasma insulin level. This review will discuss the anti-cancer effects of metformin and the pleiotropic mechanism.