Axin is an important negative regulator of Wnt pathway. We have reported that reduced expression of Axin could be detected in lung cancer tissues, but the mechanism is not clear. By analyzing the genomic sequence, we note that Axin gene promoter is rich in CpGs. Little is known about the methylation status of Axin gene in lung cancer. So, nested MSP and RT-PCR were used to study the methylation status and mRNA expression of Axin gene in lung cancer tissues and cell lines. The results showed that hypermethylated Axin gene promoter and reduced mRNA expression level of Axin could be detected in lung cancer tissues but not in their paired autologous normal lung tissues (P < 0.01). The hypermethylated Axin gene promoter significantly correlated with the degree of differentiation (P = 0.03), lymph node metastasis (P = 0.048) and TNM classifications (P = 0.032). Demethylation reagent 5-aza-2-deoxycytidine significantly up-regulate Axin expression in BE1 cells (with hypermethylated Axin gene promoter) but not in H460 cells (with unmethylated Axin gene promoter). MTT (3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and transwell matrigel invasion assay showed that 5-aza-2-deoxycytidine treatment inhibited cell growth and invasion more significantly in BE1 cells than that in H460 cells. Our data indicate that hypermethylated Axin gene significantly correlates with the progression of lung cancer and might serve as a new target of clinical therapy for lung cancer patients in future.