Aim of the work: to determine the role of Interleukin-10 (IL-10) polymorphism (rs 1800896) and Transforming Growth Factor-Beta-1(TGF-β1) polymorphism (509 CT) as markers for cirrhosis in Egyptian patients with chronic liver disease. Subjects and Methods: This case-control study was carried out on selected patients admitted to Tropical medicine department, Al Zahraa University Hospital during the period from March 2016 to April 2017. Genotyping of IL-10 (rs 1800896) and TGF-β1 (509 CT) polymorphisms were performed using real-time polymerase chain reaction (PCR) technique. Results: There was significant increase in IL10 and TGF β1 509 gene polymorphisms in compensated and de-compensated groups as compared to control group. Conclusion: Interleukin 10 rs 1800896 gene polymorphism and TGF β1 509 gene polymorphism are associated with risk of liver cirrhosis in patients with chronic hepatitis C virus infection. These findings could be useful for future screening for early detection of liver cirrhosis.