Conyza bonariensis (CB) is a cosmopolitan herb, family Asteraceae (Compositeae), commonly known as mrich booti or gulava previously used to cure cancer in traditional medicine. In the present study, n-hexane fraction by CB's triterpenoid constituents was assessed for their cytotoxic property using the human skin carcinoma cell line (SCC-13) and human peripheral blood mononuclear cells (PBMC). The chemo modulatory potential of CB n-hexane was evaluated against skin carcinogenesis in mice induced by (7-12-dimethylbenz(a)antheracene) DMBA and Croton oil. CB n-hexane extract was orally administered at the doses of 3, 6, and 9 mg/kg/day, and 9 mg/kg was also applied locally on mice skin for 16 weeks. The results from cell lines revealed that CB induces cytotoxicity against the SCC-13 cells (IC50=7.5 µM). It was found to be 4.05 times more selective in exerting cytotoxicity against SCC-13 than the PBMC (IC50=30.4 µM). The results from the mice model of skin carcinogenesis have shown that whole plant n-hexane extract administered via oral and topical routes, both reduced the number of precancerous skin papillomas and their incidence. At these concentrations, CB n-hexane also augmented the actions of catalase and superoxide dismutase, glutathione content and reduced the skin lipid peroxidation levels. These outcomes presented the cytotoxic and antioxidative effects of CB n-hexane whole plant extract and also authenticates the traditional assertions and strengthen the technical base of its chemopreventive activity.