The tuberous sclerosis (TSC) genes, TSC1 and TSC2, encode hamartin and tuberin, respectively, and are putative tumor suppressor genes that were originally identified due to their involvement in the inherited autosomal dominant disorder tuberous sclerosis. It has been elucidated that the two proteins form an intracellular heterodimer participating in signaling pathway of the mammalian Target of Rapamycin (mTOR). Recent studies showed that mTOR pathway was frequently activated in blasts from acute myeloid leukemia (AML) patient and associated with proliferation, survival, and drug-resistance of these cells. These phenomena led us to hypothesize that TSC gene might be involved in acute leukemia (AL). In this study, we investigated the TSC1 and TSC2 mRNA expression in 104 newly diagnosed AL patients and 29 healthy controls using real-time quantitative PCR (RQ-PCR) and explored the potential mechanisms of the aberrant expression through methylation-specific PCR (MSP). The results showed that the expression of TSC2 was downregulated in AL patients and the TSC2 promoter was hypermethylated which might be an important mechanism for the downregulation of TSC2 expression.