Regular coffee consumption can have preventive beneficial effects on several types of metabolic diseases and some types of cancer. In particular, the protective mechanisms of coffee are varied and due to several components with anti-inflammatory and antioxidant properties, in addition to caffeine. For example, polyphenols in decaffeinated coffee have a similar effect as caffeinated coffee on liver fibrosis and serum levels of liver enzymes, while diterpenes, exerting detoxifying action and antioxidant activity, show several benefits on liver fibrosis, cirrhosis, and cancer. The evidence for this has come from a wide variety of epidemiological studies over the past decade and remains consistent. Coffee consumption has been shown to be associated with an improvement in liver enzymes (ALT, AST, and gGT), especially in individuals at risk for liver disease, and the intake of more than 2 cups of coffee per day in patients with preexisting liver disease is associated with a slowing of the progression of fibrosis, a lower incidence and less frequent decompensation of cirrhosis, a decrease in the incidence of hepatocellular carcinoma, and lower liver-related mortality. In this chapter, we will focus on the protective health effects of coffee against hepatitis virus, liver cirrhosis, and liver cancer. We will also focus on the possible preventive and/or therapeutic actions of coffee on liver function.