Both diabetes mellitus (DM) and cancer are multifarious, dissimilar, and long-lasting, fatal diseases with a remarkable influence on health worldwide. DM is not only related to cardiovascular diseases, neuropathy, nephropathy, and retinopathy, but also related to a number of liver diseases such as nonalcoholic fatty liver disease, steatohepatitis, and liver cirrhosis. Recently, it is hypothesized that DM has a greater risk for many forms of cancer, such as breast, colorectal, endometrial, pancreatic, gallbladder, renal, and liver cancer including hepatocellular carcinoma (HCC). Both DM and cancer have many common risk factors, but the association between these two is poorly stated. Several epidemiologic studies have revealed the association between pathogenic and prognostic characteristics of DM and a higher incidence of HCC, thus representing DM as an independent risk factor for HCC development.

The etiological and pathophysiological relationship between DM and HCC has been presented in this review by linking hyperglycemia, hyperinsulinemia, insulin resistance, and activation of insulin-like growth factor signaling pathways and pharmacological management of HCC associated with DM.