Objective To compare the therapeutic effects of holmium laser lithotripsy combined with ordinary flexible ureteroscope sheath and flexible negative pressure suction sheath for urinary system stones. Methods A total of 120 patients with urinary system stones who underwent treatment in our hospital from April 2023 to August 2025 were selected. All study subjects were divided into two groups based on different treatment methods, namely an observation group （holmium laser lithotripsy combined with flexible negative pressure suction sheath） and a control group （holmium laser lithotripsy combined with ordinary flexible ureteroscope sheath）, with 60 cases in each group. Surgical indicators, stone clearance rate, postoperative pain level [visual analog scale （VAS） score], inflammation indicators （white blood cell count, C-reactive protein）, and incidence of postoperative complications were compared between the two groups of patients. Results The surgical time, sheath insertion time, and sheath removal time in the observation group were significantly shorter than those in the control group （P<0.05）; the one-time stone clearance rate of the observation group patients was significantly higher than that of the control group （P>0.05）; the postoperative residual stone rate, VAS score, white blood cell count, C-reactive protein level, and total incidence rate of complications of the observation group were lower than those of the control group （P<0.05）. Conclusion The combination of flexible negative pressure suction sheath and ureteroscopic holmium laser lithotripsy can improve surgical efficiency and stone clearance rate, reduce postoperative pain and inflammatory response, and lower the incidence of complications in the treatment of urinary system stones, showing good safety and significant clinical application value.