HEPATITIS C virus (HCV) infection is considered a major public health problem all over the world, especially in Egypt. Blood is almost the only route for HCV diagnosis. It has been reported that HCV could be detected in body fluids including saliva which represents an easier route than blood especially in infants and children. This study aimed to: 1) Assess the prevalence of HCV infection among high risk group of Egyptian children. 2) Evaluate the detection of HCV antibodies (anti-HCV) and HCV RNA in saliva against their detection in serum among HCV positive children. Patients and methods: this study included 200 children (92 males and 108 females) who were attendants of Haematology Clinic at Abu El-Reish Hospital, Faculty of Medicine, Cairo University, they were receiving frequent blood transfusions during their treatment. Serum and saliva samples were analyzed for detection of anti-HCV by ELISA technique and for HCV RNA by a home made RT-PCR method. Liver function tests were performed also. Results of serum samples revealed that 134/200 (67%) children were anti-HCV seropositive, out of them 79/134 (59%) children had HCV RNA in their sera. Saliva samples of HCV infected children (n=79) showed that 53/79 (67.1%) and 31/79 (39.2%) were anti -HCV and HCV RNA positive, respectively. Prevalence of HCV infection was 39.5% of 200 studied children. We can conclude that: 1) Prevalence of HCV infection among the studied children is considered high. 2) Saliva could play a possible role of biological fluids as a non parenteral route of intrafamilial spread of HCV infection. 3) More sensitive techniques could be developed to use saliva as a reliable route for HCV detection.