Objective To analyze the effects of microchannel percutaneous nephrolithotomy (MPCNL) and flexible ureteroscopic lithoripsy (FURL) on 2-4cm kidney stones.Methods A total of 102 patients with 2-4 cm kidney stones admitted to the hospital were enrolled from June 2021 to March 2023, including 52 cases in MPCNL group (MPCNL) and 50 cases in FURL group (FURL). The hospitalization time, operation time, intraoperative blood loss, stone clearance rate, levels of renal function indexes ［serum creatinine (Scr), blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL)］ and inflammatory factors ［white blood cell (WBC), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α)］, and occurrence of complications at 1 month after surgery in the two groups were compared.Results The hospitalization time in FURL group was shorter than that in MPCNL group, operation time was longer than that in MPCNL group (P<0.05), and intraoperative blood loss was less than that in MPCNL group (P<0.05). At 1 month after surgery, there was no difference in stone clearance rate between the two groups (P>0.05). At 3d after surgery, NGAL in FURL group were higher than those in MPCNL group (P<0.05), while BUN and Scr was lower than that in MPCNL group (P<0.05). At 3d after surgery, levels of serum WBC, CRP and IL-6 in FURL group were lower than those in MPCNL group (P<0.05). There was no significant difference in TNF-α level between the two groups (P>0.05). At 1 month after surgery, incidence of complications in FURL group was lower than that in MPCNL group (P<0.05).Conclusion MPCNL and FURL have the same stone clearance rate. However, the latter can shorten hospitalization time, reduce average length of stay and intraoperative blood loss, relieve inflammatory response and renal injury, and reduce complications in patients with 2-4cm kidney stones