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Introduction Globally, in 2015, an estimated 71 million people represented 1% of the world’s population including 5 million children, were living with chronic HCV infection, with the highest prevalence in the WHO Eastern Mediterranean region and the European region. Aim Primary objective was to assess the frequency of neurocognitive dysfunctions in children and adolescent with chronic HCV infection. Subject and Methods This prospective case–control study included forty adolescents with HCV recruited from the regular attendants of the Pediatrics Hospital, Ain Shams University and 20 healthy children from outpatient clinic. Psychiatric interviews and assessments were conducted by experienced qualified psychologist. Results Twenty adolescent with chronic HCV infection who fulfilled the inclusion criteria, were treatment naïve were recruited (Group1). They were five girls (25%) and fifteen boys (75%), their mean ages were 13.6 ± 2.37 years, were assessed before receiving Daclatasvir/Sofosbuvir, orally direct antiviral agents. They had statistically significant lower performance IQ and its subsets, verbal IQ and its subsets and total IQ as well as higher level of conduct, socializes aggression, attention problem, psychotic behavior, depression inventory and anxiety scale than control. Conclusion HCV may play a major role in cognition affection and the effect was more pronounced on the untreated HCV patients.