Growing evidence shows that obesity plays an important role on changing incidence pattern of gastrointestinal (GI) cancers during the past decades. Based on epidemiological and clinical evidence, we have investigated whether phenotypes of obesity, obesity related biomarkers, nutrients or diet patterns were associated with risk of GI cancers. Several obesity-related pathways have been hypothesized. Obesity-driven chronic inflammation, that involves rather diverse components such as innate immunity, adipocytokines, insulin, insulin-like growth factors and the gut microbiota, has been regarded as the crucial contributing factor. This inflammation might be mitigated by dietary phytochemicals. However, surgical procedures including anti-reflux surgery and bariatric surgery might not be able to stop the progression of GI cancers. Further work tries to elucidate in more details of underlying mechanisms in the development of obesity-related GI cancer and the targets of breaking the obesity-GI cancer link.