We aimed to compare the difference in case fatality rate between more developed and very high Human Development Index (HDI) regions, less developed and low HDI regions, and Romania. The incidence and mortality rates for digestive cancers were obtained from the IARC/WHO 2012 database. World mean mortality-to-incidence ratios registered the highest values in pancreatic cancer (0.97/0.94), and liver cancer (0.93/0.96) in males/females, respectively. The lowest values were recorded in colorectal cancer (0.48 in both sexes). Mortality-to-incidence ratios were generally higher in less developed areas, low HDI populations, and in Romania. The difference in case fatality rate between different areas showed higher variations for colorectal, gastric and gallbladder cancers, and smaller variations for esophageal, liver, and pancreatic cancers. In summary, mortality-to-incidence ratios of digestive cancers were high in 2012; higher values were registered in less developed and low HDI regions, and in Romania. Mortality-to-incidence ratios were similar in both sexes, even though the incidence was generally higher in men. Digestive cancer mortality variation suggests the necessity of finding better strategies for prevention, early diagnosis and treatment of digestive cancers.