Hepatocyte growth factor (HGF) is one of the adipocytokines. We evaluated whether serum levels of HGF are related to the metabolic syndrome. A total of 1474 subjects of a general population free of liver, kidney, and lung diseases received a health examination. We measured blood pressure, waist circumference, body mass index, fasting plasma glucose, lipid profiles, serum insulin, liver enzymes, and HGF concentrations. Uni- and multivariate analyses for determinant of HGF were performed. In univariate analysis, all of the components (waist circumference, triglycerides, high-density lipoprotein-cholesterol, blood pressure, and fasting plasma glucose) of the metabolic syndrome and liver enzymes were significantly related to HGF levels. By the use of multiple stepwise regression analysis, HGF levels were significantly related to waist circumference (P < 0.001), high-density lipoprotein-cholesterol (P < 0.05, inversely), and liver enzymes (P < 0.001). HGF levels were higher (P < 0.05) in proportion to the accumulation of the number of the component of the metabolic syndrome. A significant association (P < 0.05) was shown between quartiles of HGF levels and the degree of abnormality of the component of the metabolic syndrome. In conclusion, our results indicate that serum HGF levels are strongly associated with the metabolic syndrome, independent of liver function.