Background: A top ranked public health problems especially in developing countries is hepatitis C virus infection. Being asymptomatic infection, screening has been proposed as a credible public health strategy. Egyptian national guidelines were emphasizing on adopting screening programs nationwide. No economic evaluation studies tackling HCV screening based on risk exposure was conducted in Egypt so far. Aim: To evaluate the cost effectiveness of screening algorithms among two different population subgroups. Methods:  A Cost-Utility analysis was conducted using a validated decision tree model linked to a Markov Model, to compare the Incremental Cost-Effectiveness Ratio (ICER) of two policy scenarios: No screening versus Screen-and-treat with direct-acting antiviral agents (DAA) ON two Egyptian population subgroups (high risk populations of acquiring HCV infection versus the overall population). Results: The ICER for implementing screening on high-risk populations was 3895.31 EGY/ QALY, considered cost-effective (below the Egyptian Threshold 46000 EGY/ QALY). Conclusion: The ICER for implementing screening on high-risk populations was cost-effective. Whereas concerning the general population, it is considered cost-saving strategy.