Abstract: Objective: To study the SYK (Spleen tyrosine kinase) expression and mechanism of its silencing in hepatocellular carcinoma (HCC). Methods: RT-PCR (Reverse transcriptase-PCR) and MSP (Methylation- specific PCR) were used to check the expression and methylation status of SYK gene respectively, in HCC cell lines HepG2 and Hep3B and 34 paired samples of HCC tumor tissues and adjacent non- tumorous liver tissues. Results: SYK was expressed in Hep3B and was silenced in HepG2, and treatment of them with a DNA methyltransferase (DNMT) inhibitor reactivated the tran-scription of SYK in HepG2. SYK was methylated in HepG2 and unmethylated in Hep3B. In the tissues of primary tumor, the expression of SYK mRNA was negative in 5 cases and the SYK genes in all 5cases were methylated. The expression of SYK mRNA was positive in 29 cases with SYK methylation in3 cases and non SYK methylation in the other 26. Therefore, SYK gene was methylated in 23.5%(8/34)of the tumorous tissues of HCC. We also found that SYK was methylated in 8.8% (3/34) of the adjacentnon- tumorous liver tissues. Conclusion: SYK is frequently silenced through an epigenetic pathway inHCC. The aberrant SYK methylation is responsible for the loss of expression and may consequently playa permissive role in hepatocarcinogenesis.