Cancer is a complex and evolving disease that is the leading cause of death in the twenty-first century, and colorectal and liver cancers specifically are in the top 10 cancer types in terms of incidence and mortality; therefore, there has been a shift towards researching prevention strategies, amongst which chemoprevention is key. Coffee is a natural product that has recently gained importance in this area due to its chemopreventive potential and its high level of consumption worldwide. In this review, recent epidemiological and experimental evidence of the chemopreventive effect of coffee against these two types of cancer are presented, and the role of the different compounds present in coffee in cell proliferation, apoptosis and response to oxidative stress are discussed.