Chemosensitization is an effective strategy to overcome the drawbacks of arsenic trioxide (As2O3) treatment which may be possible through the use of dietary supplements in combination. Proteomic analysis revealed that the combination of arsenic trioxide with vitamins can alter a number of proteins related to the translation, cell cycle, oxidative stress and apoptotic pathways that adds to their effectiveness in the treatment of acute promyelocytic leukemia. This study provides the fact that HL-60 cells became more vulnerable to As2O3 in the presence of L-Ascorbic acid and ��-Tocopherol indicating that this combination may be a hopeful approach to increase the outcome of As2O3 in the treatment of acute promyelocytic leukemia.