Objective: To investigate the curative effects for treating condyloma acuminatum of vulva with LEEP knife combined with imiquimod cream. Methods: 138 cases condyloma acuminatum of vulva patients were randomly divided into observation group and control group with 69 cases in each group. The patients in control group were treated with LEEP knife, the patients in observation group were treated with LEEP knife combined with imiquimod cream. The total effective rate 4-week and 8-week after treatment, as well as recurrence rate and adverse effects rate of 2 groups were compared. Results: The total effective rate 8-week after treatment of patients in 2 group was all significantly higher than 4-week after treatment (P<0.05); while the total effective rate 4-week and 8-week after treatment of patients in observation group were all significantly higher than control group (P<0.05). The recurrence rate and adverse effects rate of patients in observation group were respectively 8.7% (6/69) and 60.9% (42/69), which were obviously lower than that of control group (P<0.05). Conclusions: Treating condyloma acuminatum of vulva with LEEP knife combined with imiquimod cream has the advantages of good clinical efficacy, low recurrence rate and less adverse effects, so it is worthy of application in clinic.