Regular blood transfusion puts β‐thalassemia major patients at a higher risk of developing hepatic iron overload and hepatitis C virus (HCV) infection. The association between several transfusion‐related factors and an increased risk of developing HCV viremia has been reported. The effect of HCV infection on liver damage in transfusion‐dependent thalassemia patients has been poorly described. A sample of 100 Egyptian transfusion‐dependent β‐thalassemia major children were studied. Individual patients underwent full history taking, clinical examination and a panel of laboratory tests including HCV ribonucleic acid polymerase chain reaction (HCV‐PCR) in blood samples. Liver biopsy was performed for 24 patients. HCV‐PCR was positive in 64% of patients. A statistically significant correlation was found between HCV‐PCR positivity (HCV viremia) and shorter inter‐transfusion interval. There was a significant positive correlation between mean serum ferritin level and mean levels of alanine aminotransferase and aspartase aminotransferase. Histopathologic features of both chronic hepatitis and siderosis were present in 91.7% of biopsy specimens, and fibrosis was present in 41.67%. A higher risk of HCV viremia is noted with a shorter inter‐transfusion interval. The reduced role of HCV infection in chronic liver injury in this group of patients may be surpassed by the associated effects of iron overload because of the chronic transfusion. However, the latter finding should be verified in larger studies.