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The changes of expression and function of MDM2 and P53 by MDM2 specific antisense oligonucleotides were investigated in HL60 cells. Cells were divided into control group, AS group(MDM2 specific antisense oligonucleotides group), cisplatin group, and combined treatment group.FCM analysis and Western blot and RT-PCR were used to estimate apoptosis and the expression of MDM2 and P53. Our results showed that the transfection of MDM2 specific antisense oligonucleotides obviously inhibited MDM2 expression (P＜0.01) and increased the expression of P53 (P＜0.05).Apoptosis rate were reduced by MDM2specific antisense oligonucletides and cisplatin (P＜0.01). It is concluded that MDM2 specific antisense oligonucletides can inhibit the expression of MDM2, induce the expression of P53 and increase the apoptosis of leukemia cells after chemotherapy.