Polygonatum odoratum lectin (POL), a novel mannose-binding lectin with anti-viral and apoptosis-inducing activities, was isolated from rhizomes of Polygonatum odoratum (Mill.) Druce. POL was a homo-tetramer with molecular weight of 11953.623Da per subunits as determined by gel filtration, SDS-PAGE and mass spectrometry. Based on its N-terminal 29-amino acid sequence the full-length cDNA sequence of POL was cloned. Subsequent phylogenetic analysis and molecular modeling revealed that POL belonged to the Galanthus nivalis agglutinin (GNA)-related lectin family, which acquired unique mannose-binding specificity. The hemagglutinating activities of POL were metal ion-independent, and were stable within certain range of pH and temperature alterations. Moreover, POL showed remarkable anti-HSV-II activity towards Vero cells, cytotoxicity towards human melanoma A375 cells and induced apoptosis in a caspase-dependent manner.