Hepatokines are liver-derived proteins with equivocal roles in metabolic syndrome (MetS). These proteins have prominent role in pathogenesis of MetS component such as obesity, insulin resistance, dyslipidemia and hypertension. The identification and functional characterization of hepatokines may provide significant insights that could help in better understanding of MetS pathogenesis. Fetuin-A, Hepatocyte-derived fibrinogen-related protein 1, Fibroblast growth factor 21, Angiopoietin-related growth factor, Selenoprotein-P, Angiopoietin like proteins, Leukocyte cell-derived chemotaxin 2 are regarded as the most significant hepatokines. We describe recent data on these new hormones in progression of MetS. Understanding of the accurate role of these proteins in pathophysiology of MetS can help improving prevention and treatment of this syndrome.