Semecarpus anacardium L.f. nuts is one of the best, versatile and most commonly used herbs as a household remedy, distributed in sub-Himalayan region, Tropical region, Bihar, Bengal, Orissa and central and south parts of India. In this work, the anticancer efficacy of ethanol extract of Semecarpus anacardium nuts (EESA) was tested in Swiss albino mice with induced Dalton's Ascites Lymphoma (DAL). Ethanol extract of S. anacardium nuts was given daily for 14 days at doses of 200 mg/kg and 400 mg/kg body weight, after 24 hrs of tumor inoculation. After receiving the final dose and fasting for 18 hrs, the mice were euthanized. Serum biochemical and antioxidant characteristics were measured to determine antitumor activity. 5-Fluoro Uracil, a typical medication, was employed as a positive control. In comparison to the control group, ethanol extract-treated mice restored biochemical and antioxidant parameters to near-normal levels. Biochemical and antioxidant parameters in the Dalton's Ascited Lymphoma (DAL) animal model treated with EESA exhibited similar effects as the positive control drug 5-fluorouracil. Overall, the active ingredients present in ethanol extract of Semecarpus anacardium nuts, modulate serum biochemical and antioxidant parameters and bring about anti-tumor activity against Dalton's Ascites Lymphoma (DAL) in mice.