Background: Krüppel-like factor 8 (KLF8) is a member of transcription factors. Whether and how KLF8 signaling pathways contribute to Hepatocellular carcinoma (HCC) development and progression is unknown. This study investigated role of KLF8 in Hepatocellular carcinoma cell line HCCLM3 proliferation, invasiveness and Epithelial to Mesenchymal Transition (EMT). Methods: The expression of KLF8 in different liver cell lines was detected by Quantitative real-time PCR and Immunocytochemistry. We used small interfering RNA (siRNA) to down-regulate KLF8 expression in HCCLM3. The change of proliferation and invasive ability of KLF8 down-regulated HCCLM3 was investigated by MTT Reduction Assay and Trans-well Invasive Assay respectively. The change of proliferation, invasiveness and EMT related gene in KLF8 down-regulated HCCLM3 was evaluated by Quantitative real-time PCR. Result: KLF8 protein expressed predominantly in the nuclei of cancer cells and its expression is positively correlated with metastatic potential of these cell lines. HCCLM3 has the highest KLF8 level. Decreased KLF8 expression can notably inhibit the proliferation (p<0.001, n=6), mobility and invasiveness of HCCLM3 (p<0.001, n=8). We found that the mRNA level of N-cadherin, Fibronectin and Vimentin is much higher than that of E-cadherin in HCCLM3. The expression of Cyclin D1, Focal Adhesion Kinase (FAK) and fibroblast markers including N-cadherin and Fibronectin was obviously suppressed in KLF8 down-regulated HCCLM3. Conclusion: KLF8 plays an important role in the process of HCCLM3 proliferation, invasiveness and EMT. Background: Insulin resistance (IR) has shown to play an important role in the progression of chronic liver diseases, including liver fibrosis development and hepatocellular carcinoma. The aim of this study was to elucidate the possible mechanisms of IR on the liver fibrosis development and hepatocarcinogenesis using obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods: To induce liver fibrosis, 1.0ml/kg of pig serum was injected twice a week for 4 weeks in the OLETF and LETO rats. In the hepatocarcinogenesis model, glutathione-S-transferase placental form (GST-P)-positive pre-neoplastic lesions were induced by a single injection of 200mg/kg of diethyl nitrosamine (DEN). We also performed in-vitro studies to examine the mechanistic insights. Results: The liver fibrosis development and GST-P-positive pre-neoplastic lesions were both markedly accelerated in OLETF. In the fibrosis experiment, -smooth muscle actin-positive activated hepatic stellate cells (HSC) also increased in OLETF along with augmentation of the hepatic collagen content and transforming growth factor-b1. In the DEN model, the neovascularization was up-regulated in OLETF almost in parallel with the pre-neoplastic lesions development and a potent angiogenic factor, the vascular endothelial growth factor. Our in-vitro study showed that both glucose and insulin stimulated the proliferation of the activated HSC and augmented the neovascularization. Conclusion: These results indicated that the IR status directly accelerated the liver fibrosis development and hepatocarcinogenesis at least partly through the stimulation of activated HSC proliferation and hepatic neovascularization, respectively, in the rat.