Background:Gastrointestinal tract cancers account for approximately one-third of cancer-related deaths. Early diagnosis and effective treatment are the most important ways to prevent cancer-related morbidity and mortality. ROMO1 has been shown to play an important role in many types of cancer. However, the biological function of ROMO1 is still poorly understood in gastrointestinal system cancers. The aim of this study is to reveal the expression change and oncogenic role of ROMO in gastrointestinal system cancers. Methods:Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, TIMER, GeneMANIA, TISIDB and STRING were applied to assess the biological function of ROMO1 in gastrointestinal cancers (Colon adenocarcinoma (COAD), Esophageal carcinoma (ESCA), Liver hepatocellular carcinoma (LIHC), Pancreatic adenocarcinoma (PAAD), and Stomach adenocarcinoma (STAD)). Results:ROMO1 is significantly increased in gastrointestinal cancers and overexpression of ROMO1 was associated with clinicopathological features. In addition, ROMO1 has been found to be closely associated with between tumor-infiltrating immune cells in gastrointestinal cancers. ROMO1 is closely related to the inner mitochondrial membrane proteins (TIMM) family. Conclusison: The study revealed that ROMO1 is of significant clinical importance for gastrointestinal cancers and may have potential clinical utility in treatment and prognosis.