The aim of this study was to investigate the mRNA and protein expression levels of the Syk gene as well as its promoter methylation in nasopharyngeal carcinoma (NPC) cell lines. The CNE-1 (highly differentiated), CNE-2 (poorly differentiated) and NP69 (non-cancerous human immortalized nasopharyngeal epithelial cells) cell lines were used in the present study. The MS-PCR, Q-RT-PCR and western blotting methods were used to examine the Syk gene promoter methylation levels and mRNA and protein expression in the three cell lines. The promoter methylation levels in CNE-1, CNE-2 and NP69 cells were 36%, 62% and 0, respectively. The mRNA levels in CNE-1 and CNE-2 cells were 42±3.5 and 28±2% of that in NP69, respectively; the protein levels in CNE-1 and CNE-2 cells were 36±4.5 and 16±2.5 of that in NP69, respectively; the statistical differences between groups were significant. The lower differentiation levels of the NPC cell lines correlate with lower levels of mRNA and protein expression of the Syk gene, as well as higher promoter methylation levels.