Behavioral difference of cancer cells and normal cells to anticancer drugs is diverse. Debilitating side effects observed with certain chemotherapeutic and prophylactic anticancer drugs have lead to identification of natural agents that may offer protective role against the damage induced in normal cells. The present study aimed to determine the protective role of the micronutrient mineral selenium (Se) and plant product genistein (Gn) in synergy and single, against the apoptosis induced in human peripheral blood lymphocytes by the cytotoxic agents cisplatin and mitomycin C. We observed reduction in apoptotic potential of cisplatin and mitomycin C in lymphocytes by pre-treatment and post-treatment with selenium (30 μM) and genistein (100 μM). The intercellular interaction of Se + Gn in synergy is found to be more efficient in protecting lymphocytes than as individual. Moreover the beneficial results were well pronounced in pre-treatment than in post-treatment condition. The protective action of these natural compounds suggests that they might be useful immunomodulators during the course of chemotherapy and prophylaxis.