Hepatitis C virus (HCV) infection is a major cause of cirrhosis and liver cancer, and many developing countries report intermediate-to-high prevalence. However, the economic impact of screening and treatment for HCV in high prevalence countries has not been well studied. Thus, we examined the cost-effectiveness of screening and treatment for HCV infection for asymptomatic, average-risk adults using a Markov decision analytic model. In our model, we collected age-specific prevalence, disease progression rates for Egyptians and local cost estimates in Egypt, which has the highest prevalence of HCV infection (~15%) in the world. We estimated the incremental cost-effectiveness ratio and conducted sensitivity analyses to determine how cost-effective HCV screening and treatment might be in other developing countries with high and intermediate prevalence. In Egypt, implementing a screening programme using triple-therapy treatment (sofosbuvir with pegylated interferon and ribavirin) was dominant compared with no screening because it would have lower total costs and improve health outcomes. HCV screening and treatment would also be cost-effective in global settings with intermediate costs of drug treatment (~$8000) and a higher sustained viral response rate (70-80%).