BACKGROUND: Diabetes mellitus (DM) is thought to be associated with an increased risk of hepatocellular carcinoma (HCC) in some published studies. However, can we draw the conclusion that DM is a "true" independent risk factor for HCC based on these references? DATA SOURCES: MEDLINE and PubMed searches were conducted for published studies (between January 1966 and June 2009) to identify relevant articles using the keywords "diabetes", "insulin resistance" and "hepatocellular carcinoma", including "primary liver cancer". Because of the very limited number of relevant articles most were reviewed. RESULTS: This systematic review was conducted from 4 aspects: (1) the significant synergy between DM, hepatitis virus infection, and heavy alcohol consumption in HCC; (2) the role of DM independently in HCC cases while other identified risk factors were controlled or excluded; (3) obesity, DM, and nonalcoholic fatty liver disease in HCC patients; and (4) the impact of DM for the prognosis or surgical treatment in HCC patients with DM. No consensus has been reached among these studies and it is too early to draw the conclusion that DM is a "true" independent risk factor for HCC. CONCLUSIONS: DM can be regarded as a risk factor for HCC. However, whether DM itself directly predisposes to HCC or whether it is a "true" independent risk factor remains unclear. Related issues should be clarified by more research.