The aim of the present work is to study the relation between the genetic variant in codon 25 of TGF-β1 gene (Arg25Pro; 915G>C), and the PNPLA3 (I148M; C>G) variant in the PNPLA3 gene and liver fibrosis development, HCC risk, and the severity of liver disease among Egyptian patients with HCV-related liver cirrhosis. This evidence concerns the gene PNPLA3 and cirrhosis of liver.