Gastric cancer (GC) causes high morbidity and mortality in patients largely due to its invasion and metastasis.Kiss-1has been shown to be a metastasis suppressor in various malignancies. However, its clinical significance and biological functions in GC have not been thoroughly investigated. The present study investigated the association betweenKiss-1expression and its methylation status and clinicopathological features in GC.Kiss-1expression was reduced in GC and its low expression was associated with poor histological grade, lymph node metastasis and TNM III+IV stage.Kiss-1overexpression in AGS GC cells significantly inhibited cell proliferation, migration and invasionin vitro.Kiss-1knockdown promoted the proliferation, migration and invasion of HGC-27 cells. In summary, the data demonstrated that a low expression ofKiss-1played a suppressive role for the proliferation, migration and invasion of GC cells. Its expression and methylation levels were associated with the clinical progression of GC. Thus,Kiss-1is a potential diagnostic and prognostic marker as well as a new target for the treatment of GC.