Objective To investigate the efficacy of Ilizarov technique and Masquelet technique in the treatment of femoral infective nonunion. Methods The clinical data of 63 patients with femoral infective nonunion treated in our hospital from January 2014 to January 2018 were retrospectively analyzed. They were divided into Ilizarov group and Masquelet group, according to different surgical methods. The healing time, operations frequency, complications, treatment cost, treatment effects and quality of life score were compared statistically in the two groups. Results There was no significant difference in the incidence rate of complications after treatment between the two groups (P＞0.05), and the healing time in Masquelet group was significantly shorter than that in Ilizarov group (P＜0.05). There was no significant difference in the total operations frequency between the two groups (P＞0.05). However, the treatment frequency for defects was more in Ilizarov group (P＜0.05), and the treatment frequency for infections was more in Masquelet group (P＜0.05), and the treatment cost in Masquelet group was significantly lower than that in Ilizarov group (P＜0.05). The quality of life scores were increased in the two groups (P＜0.05), and the increases of quality of life score in Masquelet group was higher than that in Ilizarov group (P＜0.05). There was no significant difference in the total excellent and good rate of efficacy between the two groups (P＞0.05), but the number of patients with “ excellent ” rating of treatment effects in Ilizarov group was significantly higher than that in Masquelet group (P＜0.05). Conclusion Ilizarov technique can repair and restore long bone defect infection, has low recurrence rate and short healing time but has difficult operation and high treatment cost, and it has great influence on the daily activities of patients. Masquelet technique is suitable for patients with short bone defect length and sufficient autogenous bone supply, and it has good safety but has high requirements for soft tissues. Therefore, the doctor should reasonably choose the clinical operation methods according to the actual situation of patients so as to help patients with good rehabilitation.