It was estimated that from 2002 to 2008 the risk of developing cancer increased a quarter-fold in men and twofold in women due to excessive BMI.Obesity,metabolic syndrome and type 2 diabetes mellitus are strictly related and are key pathogenetic factors of non-alcoholic fatty liver disease(NAFLD),the most frequent liver disease worldwide.The most important consequence of the“metabolic epidemics”is the probable rise in the incidence of hepatocarcinoma(HCC),and NAFLD is the major causative factor.Adipose tissue is not merely a storage organ where lipids are preserved as an energy source.It is an active organ with important endocrine,paracrine,and autocrine actions in addition to immune functions.Adipocytes produce a wide range of hormones,cytokines,and growth factors that can act locally in the adipose tissue microenvironment and systemically.In this article,the main roles of insulin growth factor(IGF)-1 and IGF-2 are discussed.The role of IGF-2 is not only confined to HCC,but it may also act in early hepato-carcinogenesis,as preneoplastic lesions express IGF-2 mRNA.IGF-1 and IGF-2interact with specific receptors(IGF-1R and IGF-2R).IGF-1R is over-expressed in in vitro and in animal models of HCC and it was demonstrated that IGF ligands exerted their effects on HCC cells through IGF-1R and that it was involved in the degeneration of pre-neoplastic lesions via an increase in their mitotic activity.Both IGF-2R and TGFβ,a growth inhibitor,levels are reduced in human HCC compared with adjacent normal liver tissues.Another key mechanism involves peroxisome proliferator-activated receptor(PPAR)γ.In in vitro studies,PPARγinhibited various carcinomas including HCC,most probably by regulating apoptosis via the p21,p53 and p27 pathways.Finally,as a clinical consequence,to improve survival,efforts to achieve a“healthier diet”should be promoted by physicians and politicians. It was estimated that from 2002 to 2008 the risk of developing cancer increased a quarter-fold in men and twofold in women due to excessive BMI.Obesity, metabolic syndrome and type 2 diabetes mellitus are strictly related and are key pathogenetic factors of non-alcoholic fatty liver disease (NAFLD), the most important liver disease worldwide. the most important consequence of the “metabolic epidemics” is the probable rise in the incidence of hepatocarcinoma (HCC), and NAFLD is the major causative factor. Adipose tissue is not merely a storage organ where lipids are preserved as an energy source. It is an active organ with important endocrine, paracrine, and autocrine actions in addition to immune functions. Adipocytes produce a wide range of hormones, cytokines, and growth factors that can act locally in the adipose tissue microenvironment and systemically. In this article, the main roles of insulin growth factor (IGF) -1 and IGF-2 are discussed. The role of IGF-2 is not only confined to HCC, but it may a lso act in early hepato-carcinogenesis, as preneoplastic lesions express IGF-2 mRNA. IGF-1 and IGF-2interact with specific receptors (IGF-IR and IGF-2R) models of HCC and it was demonstrated that IGF ligands exerted their effects on HCC cells through IGF-1R and that it was involved in the degeneration of pre-neoplastic lesions via an increase in their mitotic activity. But IGF-2R and TGFβ, a growth inhibitor, levels are reduced in human HCC compared with adjacent normal liver tissues. Another key mechanism involves peroxisome proliferator-activated receptor (PPAR) γ. In vitro studies, PPARγ inhibitor of various carcinomas including HCC, most probably by regulating apoptosis via the p21, p53 and p27 pathways .Finally, as a clinical consequence, to improve survival, efforts to achieve a “healthier diet ” should be promoted by physicians and politicians.