The disability-adjusted life-years caused by hepatic, gastric and esophageal cancers in mainland China are among the highest in the world. During the past four decades, improvements in primary prevention of these cancers, particularly in the isolation of risk factors, have been a nationwide goal, and secondary prevention has also been advanced. Nationwide primary preventative measures, including active vaccination against hepatitis B virus in neonates, consensus on screening and eradication of Helicobacter pylori, and quality improvement of dietary and drinking water, have been performed. Additionally, serum alpha-fetoprotein and endoscopic screening were developed and implemented as efficient secondary preventative measures for early diagnosis. Substantial strides toward cancer prevention were taken and have resulted in improved risk factors identification and more efficient screening in mainland China. Despite a reduction, HBV prevalence remained relatively high, potentially contributing to the increase in hepatic cancer-induced mortality. Because the slight decrease in H. pylori prevalence was not associated with an increase in the proportion of early diagnosis of gastric cancer, gastric cancer mortality appeared stable. Esophageal cancer incidence and mortality was reduced, principally due to the improvement in dietary habits and quality, as well as nutritional status. Nationwide isolation of risk factors and the implementation of high-risk candidate screening have been useful approaches to control mortality due to hepatic, gastric and esophageal cancers, and must be continued to secure a future reduction in mortality.