Polygonum cuspidatum is widely used as a medicinal herb in Asia. In this study, ethanol and ethyl acetate extracts of P. cuspidatum root were assayed for their 1,1-diphenyl-2-hydrazyl (DPPH) and hydroxyl free radical scavenging activities, total phenolics content, protective effect against DNA damage, and antiproliferative activity on human lung cancer cells. The ethanol and ethyl acetate (lipophilic phase) extracts of P. cuspidatum had significant scavenging effects on DPPH and hydroxyl radicals. Total phenolics content of ethanol and ethyl acetate (lipophilic phase) extracts of P. cuspidatum were 276.78 +/- 39.31 and 231.73 +/- 5.04 mg/ml, respectively; both extracts protected against hydroxyl radical-induced DNA strand scission. Furthermore, the extracts of P. cuspidatum induced apoptosis and inhibited cell growth in A549 and H1650 cell lines, suggesting that P. cuspidatum root extracts exhibit an antiproliferative effect on human lung cancer cells.