Human leucocyte antigens (HLA) class II appear to play an important role in the individual's immune response to viral infection. The aim of this study is to assess the relationship between HLA class II antigens with the clinical, laboratory and histopathological state of the liver in Egyptian children and adolescents with chronic hepatitis C virus (HCV) infection.The study included 46 chronically infected HCV children and adolescents without - hepatitis B virus (HBV) nor human immunodeficiency virus - (HIV). Their mean age was 10.4±4.23years (3-17). HLA-DRB typing was done by polymerase chain reaction (PCR) for the patients and 20 control subjects. Biochemical and haematological parameters were assessed as well as a liver biopsy was taken from the included patients.The most frequent alleles demonstrated among patients were DRB1∗03, DRB1∗04 and DRB1∗13 (45.6%, 39.1% and 26.1%), respectively. Analysis of DRB1 frequencies between patients and control revealed that DRB1*15 is significantly reduced among patients when compared with the control group (p<0.01). Patients possessing the allele DRB1*03 had significantly reduced platelet count (p=0.03), and this allele was presented to a greater extent in patients with minimal grade of inflammation. Patients with DRB1*04 had significantly low serum albumin (p=0.04) and patients with DRB1*13 had significantly high serum aspartate aminotransferase (AST) levels (p=0.05).In Egyptian HCV-infected children, special HLA patterns were found; HLA DRB1*03 was present in nearly half of the patients, while the frequency of HLA DRB1*15 was significantly reduced among the cases in comparison to the control subjects.