Background Cure of chronic hepatitis C (HCV) in HIV/HCV co-infected patients is a priority due to their increased risk of complications. Daclatasvir and sofosbuvir treatment regimens with or without ribavirin are considered an important chance for better HCV treatment in patients with HIV/HCV co-infection. This study aimed at the assessment of safety and efficacy of sofosbuvir-daclatasvir treatment regimens in HIV/HCV co-infected Egyptian patients. Results Thirty HIV/HCV co-infected adult patients were included. All patients completed the study duration without major problems or drug interactions, HCV PCR was negative for all patients at the end of treatment, yet 12 weeks after ending treatment, only one patient (3.33%) had HCV relapse. Liver enzymes showed a significant decrease by the end of treatment and 12 weeks after end of treatment in comparison with their values before treatment (P-value = 0.0001). CD4 counts as well showed significant increase. There was non-significant change in serum albumin, total bilirubin, alfa fetoprotein, complete blood count (CBC), coagulation profile, random blood sugar, or serum creatinine. Ultrasonographic findings did not show significant difference. Conclusion Combination of daclatasvir and sofosbuvir have showed 96.67% sustained virologic response at 12 weeks after treatment (SVR 12) among HIV/HCV co-infected patients, with a good safety profile. Moreover, the treated patients showed a significant increase in CD4 lymphocytic count.