Objective To investigate the clinical effect and safety of sofosbuvir-based regimens in the treatment of hepatitis C virus (HCV) -associated glomerulonephritis (HCV-GN) . Methods A retrospective analysis was performed for the clinical data of 5 patients with HCV-GN who were given sofosbuvir-based antiviral therapy in The Second Affiliated Hospital of Xi'an Jiaotong University from April2015 to October 2018, and their clinical outcome and safety were analyzed. The patients were evaluated in terms of sustained virologic response at 12 weeks after treatment ended (SVR12) , changes in liver/renal function and urinary protein during and after treatment, and safety.Results Five patients were enrolled, with an age of 27-81 years. There were 4 male patients, among whom 2 had liver cirrhosis. Of all patients, 4 had genotype 1 b and 1 had genotype 2 a. Renal biopsy was performed for 2 patients, who were diagnosed with membranoproliferative glomerulonephritis and mesangial proliferative glomerulonephritis, respectively. Of all patients, 2 received sofosbuvir + ribavirin, 2 received ledipasvir/sofosbuvir, and 1 received sofosbuvir/velpatasvir for 12 or 24 weeks. All 5 patients achieved SVR12. There were significant reductions in alanine aminotransferase and 24-hour urinary protein excretion from baseline to the end of treatment and 12 weeks of follow-up, with a slight increase in serum albumin. Blood urea nitrogen and serum creatinine were improved or showed no change. Only 1 patient experienced adverse gastrointestinal events associated with ribavirin. Conclusion Sofosbuvir-based regimens have good clinical effect and tolerability in patients with HCV-GN. Long-term follow-up should be performed to evaluate the long-term prognosis of renal disease after HCV clearance.