Many anticarcinogenic drugs kill tumour cells by inducing apoptosis. We examined the effects of hydrogen peroxide (H₂O₂) on arsenic trioxide (As₂O₃)‐induced cell killing. Low concentrations of H₂O₂ (200 μmol/l) inhibited the ability of As₂O₃ to induce apoptosis in the Burkitt's lymphoma cell line Raji. H₂O₂ altered the form of cell death from apoptosis to pyknosis/necrosis and also lowered the degree of cell killing by As₂O₃. H₂O₂ was capable of preventing caspase‐3 activation induced by As₂O₃ in Raji cells. Incubation of cells with a phosphoinositide‐3 kinase (PI‐3K) inhibitor, wortmannin (100 nmol/l), blocked the effects of H₂O₂ on As₂O₃‐induced caspase‐3 activation. In addition, the PI‐3K inhibitor partially blocked the effects of H₂O₂ on up‐regulation of Bcl‐2 and Bcl‐X_L protein expression, down‐regulation of Bax protein expression, and phosphorylation of Bcl‐2 and IκBα. This investigation demonstrated for the first time that low concentrations of H₂O₂ provide protection against the in vivo of As₂O₃‐induced apoptosis. PI‐3K plays a crucial role in enhancing cell survival during H₂O₂, inhibiting As₂O₃‐induced apoptosis in the Burkitt's lymphoma cells. As₂O₃‐induced cancer cell apoptosis may be enhanced by certain antioxidants in the treatment protocol.