Herein we report a novel peptide (named as E5) by cell-based selection from the de novo designed peptides and investigated its inhibitory effect on CXCR4/CXCL12 axis in multiple human acute myelocytic leukemia cell lines, including acute promyelocytic leukemia cell of HL-60 and NB4, acute monocytic leukemia cell of THP-1 and myelomonocytic leukemia cell of U937. The gene discussed is CXCR4; the disease is acute myeloid leukemia.