OBJECTIVE: Gastrointestinal (GI) cancers account for one-third of global cancer mortality, with nearly half being preventable. This study updates the global burden of GI cancers attributed to major risk factors. METHODS: We utilized data from the Global Burden of Disease Study 2021 to examine trends in death and age-standardized death rates related to GI cancers caused by smoking, alcohol, high body mass index (BMI), and high fasting blood glucose (FBG) from 2000 to 2021. Trends were analyzed based on countries' developmental status using a sociodemographic index (SDI). RESULTS: In 2021, there were 1.12 million GI cancer deaths related to smoking, alcohol, high BMI, and high FBG, which was 53.6% higher than in 2000. The largest proportion of GI cancer mortality was attributed to smoking (43.3%), followed by alcohol (20.6%), high FBG (20.5%), and high BMI (15.6%). The increases in GI cancer deaths between 2000 and 2021 were related to high BMI (+102.54%) and FBG (+107.69%), particularly in liver and pancreatic cancer. In 2021, GI cancer mortality in low, low-middle, and middle SDI countries represented 44.3% of the global GI cancer mortality attributed to smoking, 41.9% for alcohol, 34.3% for high BMI, and 31.6% for high FBG. Since 2000, these proportions have increased by +4.5% for smoking, +7.6% for alcohol, + 12.3% for high BMI, and +6.4% for high FBG. CONCLUSION: From 2000 to 2021, GI cancer mortality increased substantially, driven primarily by obesity and alcohol. Lower SDI countries are increasingly contributing to the global GI cancer burden.