Src homology 2 domain containing (SHC) is a proto-oncogene which mediates cell proliferation andcarcinogenesis in human carcinomas. Here, the SHC SH2-domain binding protein 1 (SHCBP1) was firstestablished to be up-regulated in human hepatocellular carcinoma (HCC) tissues by array-base comparativegenome hybridization (aCGH). Meanwhile, we examine and verify it by quantitative real-time PCR and westernblot. Our current data show that SHCBP1 was up-regulated in HCC tissues. Overexpression of SHCBP1 couldsignificantly promote HCC cell proliferation, survival and colony formation in HCC cell lines. Furthermore,knockdown of SHCBP1 induced cell cycle delay and suppressed cell proliferation. Furthermore, SHCBP1 couldregulate the expression of activate extracellular signal-regulated kinase 1/2 (ERK1/2) and cyclin D1. Together,our findings indicate that SHCBP1 may contribute to human hepatocellular carcinoma by promoting cellproliferation and may serve as a molecular target of cancer therapy.