Objective: To investigate the effect of percutaneous nephrolithotomy combined with ureteroscopic holmium laser lithotripsy in the treatment of complicated renal calculi. Methods: A total of 100 patients with complicated renal calculi admitted to our hospital from Dec. 2018 to Dec. 2020 were selected. Fifty patients treated with percutaneous nephrolithotomy in our hospital from Dec. 2018 to Dec. 2019 were included in the control group. Fifty patients treated with percutaneous nephrolithotomy combined with ureteroscopic holmium laser lithotripsy from Jan. to Dec. 2020 were included in the observation group. The stone clearance rate, complications, kidney injury indicators [serum creatinine (Scr), glomerular filtration rate (GFR), UREA (UREA), serum cystatin C (Cys-C), kidney injury mol. 1(KIM-1)] were compared between the two groups after treatment. Results: Three days after surgery and one month after surgery, the stone clearance rate of observation group was higher than that of control group, and the difference was statistically significant (P<0.05). After treatment, the incidence of complications in the observation group was lower than that in the control group, and the difference was statistically significant (P<0.05). 2 wk after operation, the levels of Scr, GFR, UREA, Cys-C and KIM-1 in observation group were lower than those in control group, with statistical significance (P<0.05). Conclusion: Compared with percutaneous nephrolithotomy alone, percutaneous nephrolithotomy combined with ureteroscopic holmium laser lithotripsy can improve the calculus clearance rate, reduce the probability of complications, and reduce the degree of kidney injury in patients with complicated renal calculi.