Galanthus nivalis agglutinin (GNA)-related lectin family, a superfamily of strictly mannose-binding specific lectins, has been well-known to possess several biological functions including apoptosis-inducing activities. However, the precise mechanisms of GNA-related lectins to induce apoptosis remains to be clarified. In this study, we showed that Polygonatum cyrtonema lectin (PCL) and Ophiopogon japonicus lectin (OJL), the two mannose-binding GNA-related lectins, could induce murine fibrosarcoma L929 cell apoptosis. In addition, we found that there was a close link between their sugar-binding and apoptosisinducing activities. Interestingly, we further confirmed that the mechanism of lectin-induced apoptosis was a caspase-dependent pathway. Moreover, we found that the two lectins could amplify tumor necrosis factorα (TNFα)-induced apoptosis. Taken together, these findings would open a new perspective for GNA-related lectins as potential anti-tumor agents.