Objective To explore the safety and perioperative management of percutaneous nephrolithotomy in the treatment of complex renal calculi with HIV infection. Methods From January 2010 to March 2020，68 patients with complex nephrolithiasis and HIV infection underwent percutaneous nephrolithotomy，and their clinical data were analyzed retrospectively. Results 62 patients received primary lithotripsy，with a clearance rate of 91.17%（62/68）；and one of whom received secondary lithotripsy. The surgical duration was（93.62 ± 10.64）min， the intraoperative bleeding volume was（145.23 ± 21.32）ml，the length of hospital stay was（5.2 ± 2.7）d，and the total complication rate was 17.65%（12/68）. There was no significant difference in CD4 + T lymphocyte count between pre⁃operation and one day after surgery in 68 patients（P > 0.05）. There were no significant differences in inflammatory indexes（leukocyte，platelet，and CRP）before and after the procedure（P > 0.05）. Conclusions Sufficient preoperative assessment for immune function，full preparation for perioperative period，and strict intraop⁃ erative protection measure and abidance by the rules of surgical procedures can provide safety guarantee for doctors and the patients with complex nephrolithiasis and HIV infection undergoing percutaneous nephrolithotomy. Better efficacy will be achieved.