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PURPOSE To describe the feasibility of computed tomography (CT)-ultrasound image fusion technique on guiding percutaneous kidney access in vitro and vivo. MATERIALS AND METHODS we compare CT-ultrasound image fusion technique and ultrasound for percutaneous kidney puncture guidance by using an in vitro pig kidney model. The fusion method, fusion time, ultrasound screening time, and success rate of puncture were compared between the groups. Next, patients with kidney stones in our hospital were randomized in the study of simulated puncture guidance. The general condition of patients, fusion method, fusion time, and ultrasound screening time were compared between the groups. RESULTS A total of 45 pig models were established, including 23 in CT-ultrasound group and 22 in ultrasound group. The ultrasound screening time in CT-ultrasound group was significantly shorter than that in ultrasound group (P < .001). In addition, the success rate of puncture in CT-ultrasound group was significantly higher than that in ultrasound group (P =.015). Furthermore, in simulated PCNL puncture study, baseline data including age, BMI, and S.T.O.N.E score between the two groups showed no statistical difference. The ultrasound screening time of the two groups was (2.60 ± 0.33) min and (3.37 ± 0.51) min respectively, and the difference was statistically significant (P < .001). CONCLUSION Our research revealed that CT-ultrasound image fusion technique was a feasible and safe method to guide PCNL puncture. Compared with traditional ultrasound guidance, CT-ultrasound image fusion technique can shorten the learning curve of PCNL puncture, improve the success rate of puncture, and shorten the ultrasound screening time.