The reappearance of HCV infection months or years after sustained virologic response (SVR) may be due to the persistence of HCV in tissue cells in spite of being undetected in serum. This situation is known as occult hepatitis C infection (OCI). We aimed to assess the prevalence of OCI in Egyptian patients with chronic hepatitis C (CHC) who achieved SVR after treatment with direct-acting antiviral agents (DAA). We carried out a cross-sectional study at the Advanced Center for Liver Diseases of Zagazig University Hospitals and Al-Ahrar Viral Hepatitis Treatment Center, Sharkia Governorate, Egypt. One hundred and fifty adult patients with CHC, who achieved SVR 12-24 weeks after end of treatment with sofosbuvir/daclatasvir ± ribavirin (139 patients, 92.67%), sofosbuvir/ledipasvir ± ribavirin (eight patients, 5.33%), sofosbuvir/simeprevir (two patients, 1.33%), and ombitasvir/ paritaprevir/ ritonavir + ribavirin (one patient, 0.67%), according to SUMMARY the Egyptian National Committee for Control of Viral Hepatitis, were included in the study. We tested these patients for HCV RNA in peripheral blood mononuclear cells (PBMCs) immediately after confirmation of SVR12-24 weeks. Statistical analysis was performed by means of the Shapiro-Wilk test, Mann-Whitney U test, Chi-square test, and Fisher’s exact test. Seventeen patients (11.33%) were positive for PBMNCs HCV RNA. The prevalence of OCI was highest in patients treated with simeprevir/sofosbuvir (2/2 patients). There is a substantially high prevalence of OCI after treatment with DAAs. We recommend dual testing for HCV RNA in both serum and PBMCs at the end of treatment of HCV infection with DAAs and during validation of the SVR following the initial response.