Aim. To assess the clinical, biochemical, and genetic risk factors for the development of hepatocyte cytolysis syndrome in patients with a combination of fatty liver disease and recrudescence of chronic cardiovascular pathology. Material and methods. The study included 74 patients with chronic cardiovascular disease (coronary heart disease, chronic heart failure, hypertension) treated in the cardiology department of the Central Clinical Hospital of the Siberian Branch of Russian Academy of Sciences with a normal baseline transaminase level (AST and ALT); 12 of them have increasing of transaminase level on 10-12 days. All patients underwent therapeutic and diagnostic procedures in accordance with the medical standards in Russian Federation. Genotyping of polymorphic loci of the genes of the cytochrome P450 family was carried out using real-time polymerase chain reaction (PCR). Results. There was no significant correlation between cytolysis syndrome and phenotypic characteristics: gender, age, body mass index. A positive correlation of fatty liver disease with abdominal obesity and body mass index was confirmed. There was no significant correlation between cytolysis syndrome and clinical and biochemical risk factors: comorbidity and lipid profile. The presence of minor minor allele of cytochrome P-450 — CYP2C9, CYP2D6, CYP2C19 genes in a patient with fatty liver disease increases the risk of cytolysis syndrome during CVD therapy. Conclusion. Pharmacogenetic testing of polymorphic variants of cytochrome P-450 — CYP2C9, CYP2D6, CYP2C19 genes is advisable to recommend to patients with cardiovascular diseases and high-risk of liver disorders for a personalized approach to therapy.