Phospholipase C δ1 (PLCD1), is located at the important tumor suppressor locus 3p22. It encodes an enzyme that mediates regulatory signaling of energy metabolism, calcium homeostasis and intracellular movements. PLCD1 has been studied in some human solid tumors relating to the CpG island methylation of the gene promoter as a functional tumor suppressor. However, no such information is available in chronic myeloid leukemia (CML). In this study, we investigated PLCD1 expression in the CML K562 cell line (0/1) and 15% (2/13) of bone marrow mononuclear cells with CML by using semi-quantitative PCR. The CpG island (CGI) methylation status of the PLCD1 promoter was detected in K562 (0/1) and 56% (23/41) of CML patients by methylation-specific PCR (MSP), but not in the normal adult bone marrow mononuclear cells. Furthermore, the DNA demethylation agent 5'-aza-2'deoxycytidine restored the expression of PLCD1 in K562 cells. Functional studies showed that ectopic expression of PLCD1 in K562 cells was able to dramatically inhibit their colony formation and induce cell cycle G1 arrest, suggesting that PLCD1 acts as a functional tumor suppressor and may serve as a biomarker for possible early detection and prognosis of CML.