AbstractObjective: This study aimed to observe the methylation levels and mRNA expression of XXYLT1 and to further analyze their possible correlation with the risk of lung adenocarcinoma. Methods: Thirty patients with lung adenocarcinoma (fifteen men and fifteen women) were recruited in this study. Cancer tissues and para-carcinoma tissues were obtained from each of the patients. The expression levels of XXYLT1 mRNA were determined, and the DNA methylation status was analyzed by MassARRAY Spectrometry. The methylation data of individual units were generated by EpiTyper v1.0.5 software.Results: Among the male patients, the expression level of XXYLT1 mRNA was significantly higher in the para-carcinoma tissues compared to the cancer tissues. Meanwhile, among the male patients, the methylation rates of three CpG units (CpG_23, CpG_25, and CpG_60.61.62.63.64.65) within the XXYLT1 gene were lower in the para-carcinoma tissues compared to the cancer tissues.Conclusions: Our results show that XXYLT1 mRNA was down-regulated and methylation rates were increased in lung adenocarcinoma tissues than in para-carcinoma tissues. These suggested that methylation of XXYLT1 may have significance in the pathogenesis of lung adenocarcinoma. Additional research is required to elucidate this aspect.