OBJECTIVE: Interleukin IL-17A and IL-17F are critical cytokines involved in inflammatory processes. Genetic variations in IL-17A and IL-17F might be linked to chronic hepatitis C (CHC) and an increased risk of hepatocellular carcinoma (HCC), a cancer associated with long-term inflammation. This study aims to examine the relationship between specific polymorphisms in IL-17A (rs2275913) and IL-17F (rs763780) and their association with HCV-related HCC in an Egyptian population. METHODS: Authors conducted a case-control study involving 52 patients with chronic hepatitis C, 49 patients with HCV-related HCC, and 51 healthy controls. The study assessed the connection between the IL-17A rs2275913 and IL-17F rs763780 polymorphisms and chronic hepatitis C patients. Genotyping was performed using real-time PCR with TaqMan MGB-probe allelic discrimination. RESULTS: No significant differences in genotype and allele frequencies for IL-17A rs2275913 and IL-17F rs763780 were observed between CHC or HCC patients and control subjects. However, significant associations were found indicating an increased risk of HCC linked to CHC: the GG genotype of IL-17A rs2275913 in a recessive model (P = 0.0129); and CT and CT + CC genotypes as well as the C allele of IL-17F rs763780 (P = 0.0038, P = 0.0055 and P = 0.0277, respectively). CONCLUSION: The study identifies a significant association between IL-17F rs763780 polymorphisms and a higher risk of HCC in Egyptian patients with chronic hepatitis C. No significant correlation was found between the IL-17A rs2275913 polymorphism and either chronic hepatitis C or HCC.