Background: Hepatitis C virus (HCV) is a global public health problem. There are about 130 to 150 million people suffering from chronic HCV. The highest prevalence of HCV in the world occurs in Egypt with estimates higher than 10% among the general population. Cryoglobulins are proteins found in the blood that precipitate (clump together) in the cold and may cause inflammation and organ damage. Objectives: To evaluate effects of direct acting antivirals on cryoglobulinemia in patients infected with hepatitis C virus and studying the effect of cryoglobulinemia on treatment of HCV by DAAs. Patients and methods: This cross-sectional study included 130 HCV patients. Patients were treated with sofosbuvir 400 mg plus daclatasvir 60 mg once daily and were evaluated before and after treatment by HCV virus load, detection of cryoglobulin, hematological parameters, liver and kidney function tests,blood glucose and lipid profile. Results:The efficacy of DAA was significantly lower in cryoglobulin positive patients (88.24%) compared to cryoglobulin negatives (98.23%) (P < 0.05).The number of cryoglobulin positive patients (17/130, 13.1%) significantly decreased after treatment of HCV with DAA (6/130, 4.6%) (P < 0.05). RBS, cholesterol and triglycerides, ASTand ALT significantly improved after treatment. Conclusion: Direct acting antivirals were very effective and safe for treating HCV and its associated cryoglobulinemia. Additionally, treatment of HCV patients with DAA lead to improvement of liver function tests, lipid profile and blood glucose.