Ureteroscopic holmium laser lithotripsy has become one of the main methods of treating ureteral calculi. However, in the treatment of middle and upper ureteral calculi, ureteroscopy is difficult to operate owing to the high location of calculi. Thus, how to improve the treatment effect and reduce the stone migration has become the focus in clinical settings. On this basis, we evaluated the application effect of low-pressure perfusion combined with occluder in holmium laser lithotripsy for patients with middle and upper ureteral calculi. This retrospective study selected 107 patients with middle and upper ureteral calculi who underwent low-pressure perfusion combined with ureteroscopic holmium laser lithotripsy from January 2021 to December 2022. We excluded 7 patients who did not meet the criteria, and ultimately included 100 patients. According to whether the occluder was used during the surgery, 100 patients were divided into groups A (n = 52, occluder) and B (n = 48, without occluder). The stone-migration rate during surgery, stone-clearance rate at 3 months after surgery, perioperative indicators, postoperative complication rate, and postoperative quality of life between the two groups were compared. The stone-migration rate in group A was significantly lower than that in group B, with statistically significant difference (p < 0.05). Both groups had no significant difference in stone-clearance rate at 3 months after surgery (p > 0.05). Group A had a significantly lower index of EuroQol (EQ) Five Dimensions Questionnaire and significantly higher score of EQ-Visual Analogue Scale than group B (all p < 0.001). Compared with the simple application of low-pressure perfusion, the combined application of low-pressure perfusion and occluder in ureteroscopic holmium laser lithotripsy can effectively reduce the stone migration and improve the postoperative quality of life.