Minimally invasive (MIS) screw fixation for Hangman's fracture can decrease iatrogenic soft-tissue injury compared with conventional open approach, but increase the risk of instrumentation-related complications due to lack of anatomical landmarks. With the advantages, the intra-operative three-dimensional fluoroscopy-based navigation (ITFN) system seems to be an inherent partner for MIS techniques. The purpose of this study was to evaluate the accuracy and feasibility of MIS techniques incorporating with ITFN for treating Hangman's fracture. 20 patients with Hangman's fracture underwent C2-C3 pedicle screw fixation using ITFN. 6 patients used MIS technique, with the other 14 patients using conventional open technique. Preoperative visual analogue score (VAS) was 5.7±1.4 in CAOS-MIS group and 5.5±0.9 in CAOS-open group. Operative time, blood loss and postoperative neurovascular complications were recorded. The accuracy of screw positions was studied by postoperative CT scan. All patients were followed up for at least 6 months and the fusion status was ascertained by dynamic radiographs. The average operative time was 134.2±8.0 min in CAOS-MIS group and 139.3±25.8 min in CAOS-open group, and there was no significant difference between the two (p>0.01). The blood loss was 66.7±25.8 ml in CAOS-MIS group and 250.0±141.4 ml in CAOS-open group. Statistical difference existed with CAOS-MIS group significant less than CAOS-open group (p<0.01). A total of 80 screws were inserted. No screw-related neurovascular injury was observed. Post-operative CT scan revealed 83.3% (20/24) screws of grade 1 and 16.7% screws of grade 2 (4/24) in CAOS-MIS group, meanwhile 89.3% screws of grade 1 (50/56) and 10.7% screws of grade 2 (6/56) in CAOS-open group. There was no grade 3 screw detected. Fisher's exact test showed there was no statistical difference between these two groups (p>0.01). There was no statistical difference in pre-operative VAS between these two groups (p>0.01). Compared with the CAOS-open group (1.7±0.6), neck pain VAS at 6-month follow-up in CAOS-MIS group (0.3±0.5) was significantly lower (p<0.01). Solid fusion was demonstrated in all the cases by dynamic radiographs. So it is feasible and safe for percutaneous minimally invasive C2-C3 pedicle screw fixation for Hangman's fracture using intra-operative three-dimensional fluoroscopy-based navigation, which can also decrease the incidence of post-operative neck pain.