Many studies have demonstrated that ZNF185, a LIM domain protein, acts as a tumor suppressor in several types of tumor cell. However, the role of ZNF185 in leukemia cells remains unclear, though it is highly expressed in the cells of human blood system. In the present study, we found dramatically decreased ZNF185 expression in the acute and chronic myeloid leukemia cell line HL-60 and K562 compared with that in normal neutrophils. To explore the role of ZNF185 in the proliferation of myeloid leukemia cells, complete coding sequence of ZNF185 was cloned and transfected into K562 cells, MTT assay showed that over expression of ZNF185 in K562 cells significantly inhibited its proliferation. To explore the molecular mechanism that regulates ZNF185 expression in myeloid leukemia cells, methylation specific PCR (MSP) was performed to determine the methylation status of ZNF185 promoter in the normal PBL neutrophils, HL-60 and K562 cells. Higher methylation of ZNF185 promoter was detected in HL-60 and K562 cells than that in normal PBL neutrophils. Furthermore, treatment of K562 cells with 5-aza-CdR, a DNA demethylation agent, resulted in demethylation of ZNF185 promoter, increased ZNF185 expression and inhibited K562 cell proliferation. Our results indicate that ZNF185 promoter methylation which reduces ZNF185 expression in K562 cells and its ability to inhibit cell proliferation may be one of the molecular mechanisms that are related to the occurrence or development of chromic myeloid leukemia.