Here we demonstrate the following: CHD5 was down-regulated in human leukemia cell lines and samples, the important regulatory region of the CHD5 gene is localized 500–200 bp upstream of the transcription start site (TSS), hypermethylation was observed in these important regulatory elements, and the hypermethylation of the CHD5 promoter repressed transcriptional activity. The gene discussed is CHD5; the disease is leukemia.