Objective: To analyze the clinical efficacy of minimally invasive percutaneous nephrolithotomy (MPCNL) in the treatment of upper urinary calculi and its preventive effect on postoperative inflammatory response syndrome. Methods: Seventy-four patients with upper urinary calculi admitted from January 2017 to October 2019 were enrolled according to different treatment methods. Patients who underwent conventional ureterolithotomy were the referred group (37 cases). The patients who underwent MPCNL surgery were the experimental group (37 cases). The surgical indexes, primary stone clearance rate, visual analogue scale (VAS) score, serum inflammatory factor index and complications were compared between the 2 groups. Results: The operation time, the disappearance time of hematuria and the hospitalization time were significantly shorter in the experimental group than those in the reference group. The intraoperative blood loss and VAS scores in the experimental group were now lower than those in the reference group, and the primary stone clearance rate in the experimental group (94.59%) was significantly higher than those in the reference group (75.68%), the indexes of IL-1, TNF-α and CRP in the experimental group were significantly lower than those in the reference group. The incidence of complications in the experimental group (5.41%) was significantly lower than that in the reference group (27.03%, P<0.05). Conclusion: MPCNL can effectively reduce inflammation and pain in the treatment of upper urinary calculi. The body recovers faster, with fewer complications and significant curative effect.