Aim: The aim of the study was a comparative analysis of genotypic variants of TNF-α and CTLA-4 genes in patients with chronic hepatitis C and liver cirrhosis and their effect on the course of the disease. Materials & Methods: The material for the molecular genetic study was the peripheral blood of the examined persons. DNA isolation was carried out according to the standard procedure with some modifications and using the reagents of the “Interlab service” company (Russia). Identification of alleles of gene polymorphism was carried out using polymerase chain reaction. Results: The analysis of the effect of TNF-α gene genotypes on the course of the disease indicates an increased risk of CVHC development with both moderate and highly active course of the disease in carriers of the G/A+A/A genotype combination. Conclusion: The data obtained allow us to conclude that the carriage of the “G” allele and the combination of genotypes A/G+G/G of the-A49G polymorphism of the CTLA-4 gene are associated not only with a decrease in the risk of CVHC development, but also with a lower intensity of inflammation and fibro-formation in the liver and a high probability of favorable course of the disease.