Objective To assess the effectiveness, safety, feasibility and advantages of novel variable-mini-percutaneous nephrolithotomy (VMP) in PCNL.Methods Clinical date of 64 patients with kidney stones who received PCNL from January 2016 to February 2021 were retrospectively analyzed. The patients were divided into VMP group (n = 36) and SP group (n = 28). All procedures were performed under ultrasound guided puncture to establish a F16 ~ F20 percutaneous renal access. Holmium laser was used with VMP system (VMP group) or standard PCNL (SP group). The perioperative indexes and stone-free rate (SFR) were collected and compared between the two groups.Results All the operations were performed successfully. The average irrigation time in VMP group was significant shorter than that of SP group [(42.72 ± 29.11) min vs (74.82 ± 37.33) min, P = 0.000], the SFR in VMP group was significant higher than that of SP group (94.4% vs 75.0%, P = 0.035), the post-operative 24 h hemoglobin (Hb) change in VMP group was 11.00 (5.00，11.25) g/L, SP group was 3.00 (-3.75，13.75) g/L, there was a significant statistically difference between the two groups (P = 0.005), and post-operative hospitalization duration in VMP group significant shorter than that of SP group [(7.56 ± 2.65) d vs (9.21 ± 3.26) d, P = 0.028]. There were no statistically differences in post-operative 24 h white blood cell (WBC) and serum creatinine (SCr) between the two group (P > 0.05).Conclusion VMP can be feasibly, safely, and effectively performed in PCNL, compared with conventional PCNL, it can significantly shorten intraoperative perfusion time and postoperative hospital stay, relieve postoperative pain and reduce the risk of infection.