The suppressor of cytokine signaling 2 (SOCS2) is a member of the SOCS family and influences the carcinogenesis of multiple types of tumors. SOCS2 acts as substrate recognition subunit of a Cullin5 E3 ubiquitin ligase complex. SOCS2 binds to phosphotyrosine-modified epitopes as degrons for ubiquitination and proteasomal degradation. Its deficiency is associated with gigantism and organismal lethality upon inflammatory challenge. SOCS2, a feedback inhibitor of JAK-STAT pathways, is expressed in most primitive hematopoietic stem cells (HSC) and is upregulated in response to STAT5-inducing cytokines. SOCS2 is a STAT5b-regulated gene and one of its functions is to influence growth and development through negative regulatory effects on GH/IGF-1 pathway. SOCS2 inhibited human hepatocellular carcinoma (HCC) metastasis, and SOCS2 might provide a new potential therapeutic strategy for treating HCC.