Lin-28 homolog B (LIN28B) is overexpressed in hepatocellular carcinoma. The heterochronic gene lin-28 is a key regulator of developmental timing in the nematode Caenorhabditis elegans. Similar with lin-28 proteins, LIN28B conserves a cold shock domain and a pair of CCHC zinc finger domains. Phylogenetic analysis suggests that they might arise as a result of duplication from an ancestral gene. Overexpression of LIN28B was noted in most HCC cell lines and clinical samples. A short LIN28B isoform was also identified in non-tumor liver tissue and fetal liver. Although predominantly localized in the cytoplasm, LIN28B protein shows cell cycle-dependent nuclear translocation in Huh7 cells. Induced expression of exogenous LIN28B in a tet-off cell line promoted cancer cell proliferation.