<p>The expression of microRNAs is regulated by CpG island hypermethylation in acute myeloid leukemia (AML). MiR-34c CpG island methylation status and miR-34c expression were tested in 205 de novo AML patients and 51 healthy controls. MiR-34c-mimics were transfected into THP-1 cells lines. Then Cell viability after transfection and apoptosis were detected. Western blot was used to detected the protein expression of p53. We found the down-regulation of miR-34c was associated with hypermethylation of the neighboring CpG island, and decitabine treatment rapidly restored miR-34c expression. Hypermethylation of the miR-34c CpG island was frequently observed in primary AML patients’ bone marrow but not in healthy donors’. Hypermethylation of the miR-34c CpG island correlated with shorter overall survival and was further confirmed by multivariate analyses. AML patients who received decitabine and achieved complete remission, methylation of miR-34c CpG island significantly decreased and expression of miR-34c significantly increased. MiR-34c CpG island hypermethylation group was positively associated with the presence of P53 and TET2 mutations but inversely correlated with CEBPA. MiR-34c CpG island regulates miR-34c expression and hypermethylation of miR-34c CpG island is frequent in AML. There is positive feedback exists between miR-34c demethylation and p53 protein expression. </p>