Objective To explore the surgical technique and evaluate safety of percutaneous nephrolithotomy (PCNL) in semisupine-lithotomy position for the treatment of complex renal stone. Methods Between March 2007 and December 2011, 686 patients (474 male, 212 female; mean age, 47.7±12.9 yrs) with complex renal stone underwent PCNL in semisupine-lithotomy position. With patient in semisupine-lithotomy position, retrograde ureteral catheterization was done and under ultrasonographic guidance 16-22 F percutaneous access tract was established. A 8/9.8 F rigid ureteroscope was introduced through the access tract and using pneumatic lithotripter associated with perfusion pump renal stones were disintegrated and fragments flushed out. Operation time, blood loss, stone clearance and complications were recorded and compared with those in 340 cases who underwent PCNL in prone position during same period of time. Results PCNL in semisupine-lithotomy position was successfully completed in all cases. The mean operation time was 72.9±28.7 min which was found to be comparatively lower than that in prone position. Mean estimated intraoperative blood loss was 104.3±76.6 ml, transfusion rate was 1.31%, stone clearance was 80.6% and total complication rate was 2.62%. There were no statistically significant differences between procedures in both positions. 97.7% of patients related semisupine-lithotomy position to be comfortable which was better than that in prone group (64.1%). Conclusions PCNL in semisupine-lithotomy position for treatment of complex renal stone renders comfortable patient position. It is a safe and feasible procedure and has lower complication rate. It facilitates intraoperative anaesthesial monitoring and improves safety of surgery. It facilitates flushing out of stone fragments and has good surgical outcomes.