The aim of this study was to identify if the expression of poliovirus receptor (PVR) on the surface of acute B lymphoid leukemia (B-ALL) cells RS4:11 and SUP-B15 is modulated by epigenetic mechanism. B-ALL cell lines RS4:11 and SUP-B15 were treated with demethylation agent. Bisulfite PCR was performed to detect percentage change of the methylated CpG islands in the promoter region of PVR. In the meantime, the expression levels of PVR at the translation and transcription levels were detected by flow cytometry and RT-PCR respectively. The B-ALL cell lines were also treated with histone deacetylase (HDAC) inhibitor. The expression level of the gene mRNA and protein was detected too. The results indicated that after treated with 5-azacytidine, the hypermethylated status of PVR promoter region was partly reversed, and the expression of PVR at both mRNA and protein levels was restored in the meanwhile. HDAC inhibitor suberoylanilide hydroxamic acid could also increase the PVR expression. But there was no synergistic function between hypermethylation and HDAC as for repressing PVR transcription in B-ALL cell lines. It is concluded that the expression of PVR in B-ALL cells is modulated by epigenetic mechanisms. Treatment with corresponding inhibitors can partly restore the gene's expression in both mRNA and protein levels.