Abstract: School Refusal (SR) is a serious problem that will interfere with daily life and future of children and adolescents. To date, two ways including psychotherapy and medication are taken into consideration to treat SR. It has been reported that Cognitive Behavior Therapy (CBT) might be effective for SR. SR frequently combines with depression and anxiety and we therefore assume that fluoxetine combined with CBT may increase the efficiency of CBT for SR. Our study investigated the efficacy of CBT combined fluoxetine treatment and CBT alone for School Refusal (SR). A total of 75 patients with SR were randomized into two groups: CBT group (n = 36) and CBT plus Fluoxetine group (n = 39). Treatment was done for 12 weeks. The Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale, Clinical Global Impression-Severity scale (CGI-S) and percentage of school attendance were used for evaluation before and after treatment. The therapeutic efficacy was compared between two groups. After 12 weeks, in the CBT group, the SAS score, SDS score and CGI-S score were significantly decreased (p<0.01) and the percentage of school attendance was 72.2%; in the CBT plus Fluoxetine group, the SAS score, SDS score and CGI-S score were significantly decreased (p<0.01) and the percentage of school attendance was 82.1%. There were no significant differences in the SAS score, SDS score, CGI-S score and the percentage of school attendance after 12-week treatment between two groups (p<0.01). Our results demonstrated that the CBT combined Fluoxetine treatment has comparable therapeutic efficacy to CBT alone for SR, but was not superior to CBT alone.