Hepatocellular carcinoma (HCC) is one of the most common causes of death from cancer and is the final stage of chronic liver disease, usually occurring in patients with cirrhosis (CP). Chronic infection with hepatitis C virus (HCV) leads to progressive liver inflammation and cirrhosis because this virus specifically affects liver tissue. Previously used interferon therapy had a relatively low efficiency and very high risks of side effects. during the period of administration of interferon (iFn) schemes it was proved that elimination of the virus significantly reduced risk of liver cancer development. discovery of direct-acting antiviral (daa) drugs have revolutionized HCV therapy with virus elimination rate of more than 95 % and an excellent safety profile. However, the risk of transformation of liver cirrhosis into hepatocellular carcinoma is still high even after complete eradication of the virus. numerous studies have shown conflicting results on the possible relationship between the use of new antiviral drugs and the increase in the frequency of newly diagnosed or recurrent hepatocellular carcinoma. thus, the long-term prognosis in terms of risk for HCC development among patients with sustained virological response (sVR) remains unclear. The purpose of the study was to analyze the literature on the effect of antiviral therapy of chronic hepatitis C with interferon-containing regimens and drugs of direct antiviral action on the risk of developing or recurring hepatocellular carcinoma. Material and Methods: We analyzed publications available from PubMed, scopus, e-library, Web of science using the key words “hepatocellular carcinoma”, “chronic hepatitis C”, “direct-acting antiviral drugs”, “liver cirrhosis”, “interferons”, and “sustained virological response”. Of the 99 studies found, 21 were used to write a systematic review. Results: Eradication of the virus reduces the risks of HCC. despite reports on high risk of occurrence or recurrence of hepatocellular carcinoma in patients with cirrhosis after treatment with daas compared with interferon-containing regimens, there is not enough data confirming the direct link between the use of daas and the development of hepatocellular carcinoma. no statistically significant difference in the frequency of HCC between patients treated with interferon or daas was detected. Conclusion: Eradication of the virus is the most significant factor in the prevention of HCC; therefore, treatment of CHC should not be delayed due to the risk of HCC. Patients with liver cirrhosis require a long period of follow-up, even after successful treatment of chronic hepatitis C with daa drugs. stratification of HCC risk requires further research. © 2019 Tomsk National Research Medical Center of the Russian Academy of Sciences. All rights reserved.