Objective: To compare the treatment effects of minimally invasive percutaneous nephrolithotomy and open surgery on kidney stones. Methods: From November 2018 to November 2019, 80 patients with kidney stones who were treated in our hospital were selected and divided into two groups according to the random number table method. Each group contained 40 patients. The patients in control group were treated with open surgery while the patients in observation group were treated with minimally invasive percutaneous nephrolithotomy. The surgical indicators, rate of stone removal, and adverse events were compared between the two groups. Results: There was no statistically significant difference in surgical time between the two groups (P>0.05). Compared with the control group, the observation group had less intraoperative blood loss and shorter hospital stay, and the differences were statistically significant (P<0.05). The stone clearance rate (95.00%) in the observation group was higher than that in the control group (77.50%), and the difference was statistically significant (P<0.05). Compared with the control group, the incidence of postoperative adverse effects was lower in the observation group, and the difference was statistically significant (P<0.05). Conclusion: Minimally invasive percutaneous nephrolithotomy for kidney stones is effective in reducing the intraoperative blood loss, shortening the length of hospital stay, improving the rate of stone clearance and reducing the occurrence of adverse effects. Therefore, this treatment method should be promoted for clinical use.