Objective To explore the effects of totally tubeless percutaneous nephrolithotomy (PCNL) and conventional PCNL on stone clearance effects, levels of inflammatory factors, immune function indexes and quality of life of patients with renal calculi of diameter ≤1cm. Methods 100 patients with renal calculi who underwent selective PCNL treatment in department of urinary surgery in our hospital from January 2017 to October 2018 were selected for the study group and were divided into observation group (totally tubeless PCNL, n=54) and control group (conventional PCNL, n=46) according to different surgical methods. The operative time, intraoperative blood loss, hospital stay, decrease of postoperative hemoglobin (Hb), stone clearance rate, postoperative analgesic dose, incidence rate of postoperative complications, changes in levels of inflammatory factors ［prostaglandin E2 (PGE-2), substance P (SP), nitric oxide (NO), lipid peroxide (LPO)］, immune function indexes and SF36 quality of life scores before and after surgery were compared between the two groups. Results There were no significant differences in the operative time, intraoperative blood loss and postoperative Hb decrease between the two groups (P＞0.05). The hospital stay in observation group was significantly shorter than that in control group, and the stone clearance rate was significantly higher than that in control group, and the postoperative analgesic dose was significantly lower than that in control group (P＜0.05). There was no significant difference in the incidence rate of postoperative complications between the two groups (P＞0.05). Levels of PGE2, SP, NO and LPO in both groups were significantly increased after operation, but the levels in observation group were significantly lower than those in the control group (P＜0.05). Levels of CD+ 4and CD+4/CD+8 in both groups decreased significantly after operation while the level of CD+8 increased significantly. Changes in the observation group were smaller (P＜0.05). The postoperative SF36 quality of life score in observation group was significantly higher than that in control group (P＜0.05). Conclusion Totally tubeless PCNL has better stone clearance effects on renal calculi with diameter ≤ 1cm. It can significantly relieve postoperative discomfort and pain and reduce the analgesic dose, without increasing the risk of postoperative complications. It can reduce inflammatory stress response and immunosuppression to some extent, and improve postoperative quality of life of patients.