Cancer is one of the major causes of death in the world today. Although chemotherapeutic regimen remains the prime treatment of cancer, it is important to explore for newer compounds due to their adverse reactions and the growing rate of resistance. Traditionally, some plants are used for the treatment of cancers in India. However, no scientific data backing the evidence exists for the same. Among such plants is Cleome viscosa Linn, which is used in the Indian system of medicine for cancer treatment. To test its anticancer activity and generate scientifically reliable data, the extraction of whole plant has been carried out using methanol and fractions were generated using petroleum ether, dichloromethane, ethyl acetate and n-butanol. The fractions were first tested in vitro for their antiproliferative activity and mechanistic studies. In this paper, we report the anticancer potential of the fractions by a preliminary cytotoxicity activity in vitro using cell lines followed by the liquid tumor (EAC) model in mice. Upon screening on a panel of cancer cell lines, the fractions of petroleum ether, dichloromethane and ethyl acetate were found to possess significant cytotoxic activity on Hela and U343 cell lines. With this evidence, we have then tested the in vivo activity on mice using the liquid tumor model in which the fractions of pet ether, dichloromethane and ethyl acetate exhibit a potential anticancer activity which is evident in characteristics like inhibition of tumor progression, increase in the mean survival time and percentage increased life span along with a decrease in tumor volume. The fractions also showed significant anti-oxidant properties.