Phyllanthus urinaria (P. urinaria), a widely used herbal medicine, has been reported to possess various biological activities. This report aimed to characterize the whole P. urinaria plant, present the anticancer effects of P. urinaria both in vivo and in vitro, and explore relevant mechanisms. The water extract of P. urinaria not only significantly reduces the cell viability of various cancer cell lines from different origins but also suppresses tumor development in C57BL/6J mice after implantation of Lewis lung carcinoma (LCC) cells. The anticancer activity of P. urinaria extract is mainly due to induced apoptosis of cancer cells as demonstrated by DNA fragmentation and increased caspase-3 activity through both intrinsic and extrinsic pathways. The decrease in viability with P. urinaria treatment might be partially associated with down-regulation of telomerase activation and induction of the apoptotic process. In addition, P. urinaria also exhibits anti-angiogenic activity that is mediated, at least in part, by suppression of matrix metalloproteinase 2 (MMP-2) secretion and inhibition of MMP-2 activity through zinc chelation.