Today there is increasing evidence concerning the contribution of pro-/anti-inflammatory cytokine balance and genetic factors in hepatitis C pathogenesis and interindividual heterogeneity of disease outcome. In the current study, we investigated the influence of functionally described single nucleotide polymorphisms (SNPs) present in interferon-gamma (IFNgamma) and interleukin-10 (IL-10) genes, on chronic hepatitis C severity. IFNgamma (+874T/A) and IL-10 (-1082G/A) genotypes were determined in 100 hepatitis C patients with different disease severities (chronic hepatitis, n = 42, liver cirrhosis [LC], and hepatocellular carcinoma in liver cirrhosis [HCC], n = 58) and 103 healthy controls using allele-specific polymerase chain reaction. No statistical differences in allele or genotype distributions of IFNgamma and IL-10 genes were observed between patients and controls. However, some significant differences in IFNgamma genotype frequencies were observed between the two groups of patients. IFNgamma(high producer) genotypes TT and TA were significantly more common in patients with LC and HCC (odds ratio = 2.65; p = 0.019). Although IL-10 genotypic frequencies were comparable between the different clinical forms of the disease, the combination of IFNgamma(low producer) and IL-10(high producer) genotypes was significantly associated with a lower risk of LC and HCC (odds ratio = 0.21; p = 0.015). In conclusion, our findings suggest that the imbalance between the pro-inflammatory and anti-inflammatory responses mediated by polymorphisms in the IFNgamma and IL-10 genes may influence the outcome of chronic HCV infection.