Cytokine responses are stringently controlled by a family of proteinsSTAT3 termed the suppressors of cytokine signaling (SOCS), and deregulation of SOCS function is associated with many diseases, including several cancers, disorders in hematopoiesis, and autoimmune diseases. Our current understanding of the divergent roles of SOCS3 has recently improved and indicates that SOCS3 is critical in modulating cytokine-mediated and neoplastic-proliferative responses in the liver. The generation of hepatocyte-specific Socs3 knockout mice suggests that loss of SOCS3 expression encourages hepatocyte proliferation, survival, and hepatocellular carcinoma formation. By elucidating the regulation of pathways leading to liver regeneration we may gain useful insights to control liver disease and tumor growth.