This comprehensive analysis revealed the oncogenic role of ROMO1 in gastrointestinal tract cancers, the potential value of ROMO1 in the diagnosis of GI cancers, the underlying molecular mechanisms of ROMO1 in GI cancer pathogenesis, and the effects of ROMO1 in anti-tumor immune response and therapeutic target in the treatment of GI cancers. This evidence concerns the gene ROMO1 and digestive system cancer.