Here we reported a novel human secreted protein named as hZG16, with a Jacalin domain. Evolution analysis through comparing with the orthologs of other organisms suggested that ZG16 is a conserved gene under the purifying selection (d(N)/d(s)<1) in the evolution. Interestingly, Northern and dot blot analyses showed that hZG16 were highly expressed in adult liver, not in fetal liver, and moderately in gut, including jejunum, ileum, and colon, in which the tissue expression pattern of hZG16 was significantly dissimilar to that of mouse and rat orthologs that were uniquely expressed in spleen and pancreas, respectively. Unexpectedly, hZG16 was markedly down-regulated in hepatocellular carcinoma (HCC) as indicated by RT-PCR, Northern blot analysis and immunohistochemistry staining. However, the tunicamicin treatment and pulse-chase experiments showed that hZG16 protein had a similar molecular function with rZG16 that take part in glycoproteins' secretion in a bus mode.