It is unclear whether direct-acting antiviral drugs (DAAs) result in the complete eradication of HCV infection or whether some quantities of the virus may persist after achieving a sustained virologic response (SVR). Aim The aim of this work was to study the possibility of the persistence of HCV RNA in peripheral blood mononuclear cells (PBMCs) after achieving SVR following DAA treatment. This study included 100 patients infected with HCV genotype 4, who were candidates for receiving DAAs and who achieved SVR during follow-up, as determined at 12 and/or 24 weeks following the end of treatment. All patients were subjected to demographic, biochemical and hematological assessments. Detection of HCV RNA in the serum and PBMCs and determination of the HCV genotype were performed with real-time PCR. We detected HCV RNA in the PBMCs of 20 out of 100 (20%) patients infected with HCV genotype 4, who achieved SVR. However, the persistent viral load in the PBMCs was very low (range: 400–900 U/mL; mean ± SD: 645.45 ± 153 U/mL). Multiple logistic regression analysis showed that only the higher posttreatment levels of aspartate transaminase (AST) were significantly predictive of HCV RNA persistence in the PBMCs (OR: 1.29; 95% CI: 1.08–1.55). Additionally, according to the Cox proportional hazard model, liver cirrhosis was the only significant risk factor for the persistence of HCV infection in PBMCs (HR: 5.8; 95% CI: 1.3–26.1; P < 0.02). Our results indicated the persistence of HCV RNA in some HCV patients who achieved SVR after treatment with DAAs.