Background/Aims: Hepatocyte growth factor (HGF) responds to tumor necrosis factor- α (TNF- α) secreted by macrophages and has been suggested to function in malignant metastasis. This study was performed to shed a light on the complicated relation between intrahepatic macrophages, TNF- α, HGF and hepatocellular carcinoma (HCC) microvascular invasion (MVI) and pathological grade. Methodology: Forty-eight HCC cases were divided into three groups according to pathological grade: poorly-differentiated (PD), moderately-differentiated (MD) and well-differentiated (WD) groups. Each group was divided into subgroups based on the condition of MVI. Macrophages were counted, and TNF- α and HGF were tested in all specimens by immunohistochemical analysis and RT-PCR. Results: In peritumoural liver tissue, MVI had more HGF (t=8.22, p<0.05) and less TNF- α (t=4.20, p<0.05) than non-MVI. With MVI, PD and MD had more TNF- α (t=3.30, p<0.05and t=2.82, p<0.05) than WD in peritumoural tissue. Conclusions: Overexpressed TNF- α and HGF in microenvironment were related to poor differentiation and microvascular invasion of HCC. We suggest that inflammation of hepatic microenvironment promote pathological degradation and microvascular invasion of HCC.