Hepatitis C is a viral liver disease caused by HCV. Worldwide, 71 million people suffer from chronic hepatitis C infection. There is a discussion in the literature sources about the association of blood groups of the AB0 system with viral hepatitis; however, the data obtained in different populations of high rank is controversial. The aim of the study was to investigate possible associations of blood groups of the AB0 system with hepatitis C in the Odessa region. The case-control study was conducted in 2017–2019 at the blood transfusion station of SE «Odessa Railway». The control group consisted of 18 963 healthy individuals, the experimental group consisted of 520 people from the donors examined, in which blood antibodies to HCV were detected. Determination of blood groups was performed according to the standard method, serological studies – ELISA on ELISA analyzer III. The analysis using the χ2 criterion showed that the frequencies of blood groups in the control and experimental groups differed significantly (p ≤ 0.005). To determine the effects of each blood group, relative risk frequencies for each blood group were calculated. People with the AB blood group had the lowest risk of infection (OR = 0.60), with a slightly weaker negative association observed among people with blood group 0 (OR = 0.86). Individuals with blood groups A and B had a positive association; the rate of infection of persons with blood group B was the highest (OR = 1.23). The findings complement a diverse picture of such associations in different populations. The variation in associations in different populations may be due to both statistical causes and genetic diversity of human and HCV populations, as well as the interaction between human immunity-related genetic systems. The existence of associations between the AB0 system and susceptibility/immunity to hepatitis C may be an additional indicator of the assessment of risk groups, which is functional for certain populations in certain sanitary and epidemiological conditions.