The cytochrome P450 (CYP) family is the most important drug-metabolizing enzyme in human body and is responsible for the metabolism of endogenous and exogenous compounds. As the main site of the expression of the CYP family, the liver is the metabolic center of drugs, and in recent years, the role of the CYP family in the liver has attracted wide attention from the scholars in China and globally. This article reviews the distribution differences of the CYP family from the aspects of anatomy, genetics, and genomics, changes in the expression of the CYP family in the pathological processes such as non-alcoholic fatty liver disease, alcoholic liver disease, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma, and the effect of CYP family-mediated enzyme activity on the treatment effect of pharmacotherapy for metabolic-associated liver diseases, in order to provide important enlightenment for identifying key drug intervention targets in diseases and enhancing clinical efficacy and safety.