Chemoprevention is an important strategy to control the process of carcinogenesis. The potential of using medicinal herbs as cancer chemopreventive nutraceuticals and functional food is promising. Thus, there is a need for exploring drugs/agents which act as chemopreventive agents. Phyllanthus niruri is a well known medicinal plant which has been used in Ayurvedic medicine as hepatoprotective, antiviral, antibacterial, analgesic, antispasmodic and antidiabetic. The present study was carried out to evaluate the anti-tumor activity of a hydro-alcoholic extract of the whole plant, in 7-9 week old male Swiss albino mice, on the two stage process of skin carcinogenesis induced by a single topical application of 7, 12-dimethylbenz (a)anthracene (100µg/100µl acetone) and two weeks later promoted by repeated application of croton oil (1% in acetone/three times a week) till the end of experiment (16 weeks). The oral administration of P. niruri at a dose of 1000 mg/kg/b.wt. at peri- (i.e. 7 days before & 7 days after DMBA application) and post- (i.e. starting from the croton oil application) initiational phase of papillomagenesis caused significant reduction in tumor incidence, tumor yield, tumor burden and cumulative number of papillomas as compared to carcinogen-treated controls. Furthermore, the average latent period was significantly increased in the PNE treated group. The results thus suggest that P. niruri extract exhibits significant anti-tumor activity, which supports the traditional medicinal utilization of this plant.