Polygonatum cyrtonema (PCL) lectin is a mannose/sialic acid-binding lectin that displays significant inhibitory and cytotoxic activity toward cancer cells. Moreover, the underlying molecular mechanisms of apoptosis and autophagy are also demonstrated and our results suggest that it would be worthwhile to explore the wonderland of plant lectins in regard to cancer therapeutics. PCL was shown to markedly inhibit the growth of human melanoma A375 cells. It was also found to simultaneously induce A375 cell apoptosis and autophagy. The mechanism of apoptosis following treatment with PCL involves regulation of the Bax, Bcl-xL and Bcl-2 proteins, which then cause collapse of the mitochondrial membrane potential. PCL also abrogates the glutathione antioxidant system and induces mitochondria to generate massive ROS accumulation. PCL was additionally found to induce human melanoma A375 cell apoptosis, as evidenced by morphological and ultrastructural changes.