Objective To analyze the clinical efficacy and safety of glecaprevir/pibrentasvir in the treatment of patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection, and provide scientific basis for clinical treatment. Methods 89 initially treated non-cirrhotic patients with HCV/HIV co-infection in a hospital of Butuo County of Liangshan Prefecture from January 2021 to January 2022 were selected. All patients received glecaprevir/pibrentasvir treatment for 8 weeks and were followed up for 12 weeks. Virological response rate at the end-of-treatment and sustained virological response rate after 12 weeks (SVR12) of treatment as well as occurrence of adverse reaction were recorded. Results Among 89 initially treated non-cirrhotic patients with HCV/HIV co-infection, most were middle-aged and young married men (n=79, 88.8%). HIV was mainly transmitted through sexual contact (n=62, 69.7%) and intravenous drug use (n=27, 30.3%). The most common HCV geno-types were genotype 1b (n=33, 37.1%) and genotype 3b (n=25, 28.1%). All patients completed 8 weeks of treatment successfully and HCV RNA load at the end of treatment was below the detection limit (< 25 IU/mL). Eight patients failed to complete the follow-up, and the remaining 81 (100%) patients achieved a sustained virologic response. There were no serious adverse reactions during the observation period, but 11 patients had mild adverse reactions. Conclusion The 8-week treatment regimen of glecaprevir/pibrentasvir for non-cirrhotic patients with genotype 1, 3, and 6 HCV/HIV co-infection can achieve 100% SVR12, with high safety and tolerability, which can be used as a good choice for clinical treatment of these patients.