LOC554202 was significantly downregulated in cancerous tissues and CRC cell lines compared with adjacent normal tissue and a normal human intestinal epithelial cell line. Low LOC554202 expression was closely associated with advanced pathologic stage and a larger tumor size. The overexpression of LOC554202 decreased the cell proliferation and induced apoptosis in vitro and hindered tumorigenesis in vivo. LOC554202 regulated cell apoptosis partly through the activation of specific caspase cleavage cascades.