OBJECTIVE To investigate the methylation status of PTPL1 in Hut78, Maver, Z138, CA46, Raji and Jurkat cell lines, and the reversing effect of 5-Aza on expression of PTPL1 mRNA. METHODS The Hut78, Maver, Z138, CA46, Raji and Jurkat cell lines were cultured in vitro, the MS-PCR was used to detect the methylation status of PTPL1 gene and RT-PCR was used to detect the expression of PTPL1 mRNA, the CCK-8 method was used to determine the cell proliferation, the siRNA-mediated silencing of PTPL1 was used to clarify the role of PTPL1 in lymphoma cell lines. RESULTS PTPL1 gene promoter was non-methylated in Hut78, Maver and Z138 cells, and was hyper-methylated in Raji, CA46 and Jurkat cells; the different levels of PTPL1 mRNA expression were in Hut78, Maver and Z138; the re-expression of PTPL1 mRNA resulted from hyper-methylation was found in Raji, CA46 and Jurkat cells. The 5-Aza treatment could inhibit the prolifenation of Raji, CA46 and Jurkat cell lines and induce re-expression of PTPL1 mRNA. After PTPL1 was interfered by siRNA, the growth of lymphoma cells was promoted. CONCLUSION The PTPL1 gene silencing induced by hyper-methylation may be an important factor in the occurrence and development of non-Hodgkin lymphoma. The methylation of PTPL1 gene may be used as a possible molecular marker for diagnosis and treatment targets.