To compared the effectiveness and safety of single standard mini percutaneous nephrolithotripsy (SM-PCNL) combined with retrograde intrarenal surgery (RIRS) and multiple standard mini percutaneous nephrolithotomy (MSM-PCNL) in the treatment of octopus stone of 2 to 4 cm. The clinical data of SM-PCNL combined with RIRS and MSM-PCNL for octopus stone with a 2 to 4 cm diameter from October 2019 to December 2022 were analyzed retrospectively, and propensity score matching was used to screen patients. The matched patients were paired, and the operation time, complications, postoperative pain, tubeless rate, stone-free rate (SFR), and postoperative hospital stay were further compared between the 2 groups. 88 patients underwent SM-PCNL combined with RIRS (combined group), and 143 patients underwent MSM-PCNL (multiple channel group). After matching analysis, there were 49 patients in each group, and there was no significant difference in the general preoperative data between the 2 groups. The perioperative complications and stone-free rate were no statistical difference. In postoperative pain (4.00 ± 0.74 vs 5.00 ± 0.74, P = .00), tubeless rate (44.90% vs 20.41%, P = .01), hemoglobin drop (9.38 ± 7.48 vs 14.22 ± 7.69, P = .01), postoperative hospital stay (3.37 ± 1.09 vs 5.08 ± 1.29, P = .00), the combined group was significantly better than the multiple channel group. Regarding operation time, the combined group was more than the multiple channel group (103.27 ± 27.61 vs 78.39 ± 19.31, P = .000). For octopus stone with a diameter of 2 to 4 cm, the effectiveness and safety of SM-PCNL combined with RIRS were similar to those of MSM-PCNL The surgeon should carefully evaluate the patient's physical condition, stone characteristics, and expectations before the operation and assist the patient in choosing an appropriate plan., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)