Cancer is responsible for millions of deaths each year worldwide. Pharmacological intervention with plant-derived products alone or in combination to reverse, suppress, or prevent the cancer progression plays a key role in the fight against this terrible disease. Aerva lanata is an important medicinal plant widely used in traditional systems of medicine like ayurveda and siddha. Ethanolic extract of whole plant of A. lanata exhibited immunomodulatory and antitumor activity. Intraperitoneal administration of five doses of the extract (10 mg/kg body weight) was found to enhance the total WBC count (14,238 cells/mm(3)), bone marrow cellularity (22.33 × 10(6) cells/femur), and number of α-esterase-positive cells (1276 cells/4000 cells). Aerva treatment also showed enhanced proliferation of splenocytes, thymocytes, and bone marrow cells both in the presence and absence of specific mitogens in vitro and in vivo. The number of plaque-forming cells (PFC) in spleen (243.33 PFC/10(6) spleen cells) and circulating antibody titer were also increased (P < 0.001). The extract was 100% cytotoxic to Dalton's lymphoma ascites (DLA) and Ehrlich ascites carcinoma (EAC) cells at a concentration of 500 µg/mL. It was also found to be cytotoxic toward L929 and HELA cells at higher concentrations, whereas the nontoxic concentrations produced a reduction in the rate of proliferation. Simultaneous administration of five doses of A. lanata extract could produce significant inhibition in DLA-induced solid tumor development in mice and increase the life span of mice-bearing EAC tumors by 53.47%.