AIM: To study on antisense oligoncleotides as inhibitor of human acute promyelocytic leukemia (HL-60) proliferation and C-myc protein expression. METHODS: Oligonucleotides with different lengths (18-21 mer) complementary to the definite regions of C-myc mRNA, modified groups (with S replaced O in internucleotide phosphate linkage) and unmodified ones (with natural internucleotide phosphate linkage) were designed and synthesized. These olignucleotides were tested for their activity on HL-60 cell and also for their toxicity on normal lymphatic cells of human. RESULTS: It was found that two of the oligonucleotides complementary to 5′-44-61 and 5′-556-576 the regions of C-myc mRNA exhibited great inhibitory effects (59.5 % and 62.7 %) on growth of HL-60 cells for a definite time. And no toxicity of the two antisense oligonucleotides was found on normal lymphatic cells of human. CONCLUSION: The sequence of antisense oligonucleotides complementary to 5′-44-61 of C-myc mRNA was designed newly by us may be turned into inhibitory medicine of HL-60 cells.