Objective To investigate the aberrant methylation and expression of growth arrest and DNA-damage-in-ducible 45 gamma (GADD45G) gene in gastric cardia adenocarcinoma (GCA). Methods Bisulfite conversion-methylation specific polymerase chain reaction method (BS-MSP) and immunohistochemistry method were used respectively to detect the methylation status and protein expression of GADD45G in 138 GCA tumor tissues and corresponding normal tissues. Re-sults The methylation status of GADD45G distal promoter (region 1) was not detected in GCA tumor tissues and corre-sponding normal tissues. For GADD45G region 2 and region 3, the BS-MSP results of region 3 were identical to that of re-gion 2. The methylation frequency of proximal promoter and exon 1 in GADD45G island 2 (region 2 and region 3) in GCA tu-mor tissues (49.3%, 68/138) was significantly increased compared to that in corresponding normal tissues (0, P＜0.01). The methylation status of this two sites in tumor tissues was associated with TNM stage of tumors (P＜0.05). The protein expres-sion of GADD45G in tumor tissues was significantly decreased than that in corresponding normal tissues (P ＜ 0.05),and threre was a significant negative correlation with methylation status of GADD45G proximal promoter and exon 1 (rs=-0.398). Conclusion The decreased expression of GADD45G by hypermethylation of proximal promoter exon 1 of the gene may play an important role in gastric cardia adenocarcinoma.