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Objective: To investigate the anti-leukemic function of econazole (Ec),an azole anti-fungal drug.Methods: We compared efficacy of econazole to induce apoptosis in HL-60 cells with two other known endoplasmic reticulum (ER) stress inducer thapsigargin (Tg) and tunicamycin (Tu).Results: Cells treated with Ec showed typical morphology of apoptosis following24 h incubation,parallel to the morphological changes,the expression of molecular chaperone GRP 78 was up-regulated in all cases and the caspase 12,an ER resident caspase was activated.Conclusion: Ec induced ER stress related apoptosis in HL-60 cells; the underlying mechanisms are protein synthesis inhibition through elF2α phosphorylation and caspase 12 activation.