Introduction: The main challenge in cancer treatment is the serious side-effects due to non-specific interaction of drugs at molecular level. Arsenic trioxide has been found to be an effective anticancer drug, but it adversely affects certain organs. The protection of normal cells during chemotherapy is a challenging step. The recent research in combination therapy with natural anti-oxidants are attracting the medical attention. We evaluated the efficacy of eugenol as a protective agent to nullify the side effects of arsenic trioxide. We have studied the interaction between eugenol and arsenic at two different pHs, 4-5 and 7-8, in aqueous medium at physiological temperature (37ºC) using NMR spectroscopy. Methods: As2O3 was mixed with varying concentrations of eugenol giving varying proportions of arsenic – eugenol mixture (1:1, 1:2, 1:3 and 1:4) and 1D 1H NMR spectra of all the mixtures were recorded at two pHs, 4-5 & 7-8 and two temperatures, 20ºC & 37ºC Results & Discussions: The NMR studies showed that the antioxidant molecule eugenol interacts with the anti-cancer drug arsenic trioxide at physiological pH, but not at acidic pH. The pH specific interaction of eugenol with arsenic trioxide may protect the normal cells against the action of arsenic trioxide in normal cells. Conclusions: The protective efficacy of eugenol against arsenic trioxide is pH specific. This property can be utilized to design a combination therapy protocol for the treatment of Acute promyelocytic leukemia (APL) to reduce the side effects of arsenic trioxide. Key words: Acute promyelocytic leukemia (APL), Eugenol, pH dependence, NMR References 1. Binu, P., Priya, N., Abhilash, S., Vineetha, R. C., & Nair, R. H. Studies on curative efficacy of monoterpene eugenol on anti-leukemic drug arsenic trioxide induced cardiotoxicity. Biomedicine & Pharmacotherapy, 2017, 91, 559-566. 2. Binu, P., NellikunnathPriya, M. P. H. I. L., Abhilash, S., Vineetha, R. C., & Nair, H. Protective Effects of Eugenol against Hepatotoxicity Induced by Arsenic Trioxide: An Antileukemic Drug. Iranian journal of medical sciences, 2018, 43(3), 305.