Recent meta-analysis indicate that coffee consumption may reduce the risk for digestive tract cancers (oral, esophageal, gastric and colorectal) and, especially, liver cancer. Coffee bean-derived beverages, such as the widely-consumed espresso and "common" filtered brews, are commodities of remarkable historical, cultural and economic importance globally. These drinks display rich and variable chemical composition, depending on many factors that vary from "seeding to serving". The alkaloids caffeine and trigonelline, and the polyphenol chlorogenic acid seem to be some of the most important bioactive organic compounds of these beverages, displaying high levels in both espresso and common brews and/or increased bioavailability after consumption. Thus, we proposed a comprehensive literature overview of current knowledge on the effects of coffee beverages and their highly bioavailable compounds, describing: 1) recent epidemiological and experimental findings highlighting the beneficial effects against gastrointestinal and liver carcinogenesis; and 2) the main molecular mechanisms in these in vitro and in vivo bioassays. Findings predominantly address protective effects of coffee and its most common and bioavailable compounds individually against gastrointestinal and liver cancer development. Our review underscores the complex effects of coffee on carcinogenesis, considering that beneficial effects are not limited to the whole beverage or selected compounds. Thus, this review should provide new insights of clinical and translational significance for further mechanistic investigations.