MDS1 and EVI1 complex locus protein EVI1 (MECOM) is an oncogenic transcription factor in many types of cancer. However, the clinical significance of MECOM in esophagogastric cancer has not been well elucidated. The aim of this study was to define the association of amplification of MECOM and esophagogastric cancer patients' overall survival rate and to investigate the functional role of MECOM in MKN45 cell proliferation and apoptosis. In this study, a total of 3236 esophagus and gastric patients were analyzed from 16 genomic studies using cBioPortal, which provides an open-access resource with multiple cancer genomics data sets. When the patient samples were divided into two subgroups (MECOM amplified group and MECOM non-amplified group), the poor survival rate was significantly associated with MECOM amplification (p= 0.04). To investigate the role of EVI1 on esophagogastric cancer cells, siRNA dependent gene silencing of EVI1 in MKN45 cells was conducted. RT-PCR was used to examine the expression of EVI1 in MKN45 cells. The MTT assay was used to examine cell proliferation. The apoptotic cells were quantified by fluorescence cell counter. Knockdown of EVI1 leads to reduced cell proliferation and induced apoptosis in MKN45 cells. These results indicate that MECOM may be a potential target for esophagus and gastric cancer gene-targeted therapy. Collectively, our result suggested that EVI1 is a probable target gene for esophagogastric cancer cell proliferation.