Objective · To explore the effect of simplified cognitive behavioral therapy (SCBT) on generalized anxiety disorder (GAD). Methods · GAD patients were recruited from Shanghai Hongkou Mental Health Center, Shanghai Putuo Mental Health Center, Tenth People’s Hospital of Tongji University, The Affiliated Brain Hospital of Nanjing Medical University and Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, who were divided into SCBT group, SCBT+medication group and medication group. The Generalized Anxiety Disorder Scale-7 (GAD-7) was used to assess the patients' generalized anxiety symptoms, Hamilton Anxiety Scale-14 (HAMA-14) to assess the patients' anxiety level, and Hamilton Depression Scale-17 (HAMD-17) to assess the patients' depression level. SCBT and/or medication were used. Three groups of patients were evaluated by single blind method. Variance analysis and χ2 test were used to compare the cure rate and the severity of anxiety and depression at different time points. Results · A total of 134 cases were included in the statistical analysis, 39 cases in SCBT group, 53 cases in SCBT+medication group, and 42 cases in medication group. There was no significant difference in gender, education level and marital status among the three groups, and there was significant difference in age (P=0.033). The cure rate of SCBT group was higher than those of SCBT+medication group and medication group (P=0.005). The scores of anxiety and depression of the three groups decreased with the prolongation of treatment time. Conclusion · SCBT can effectively alleviate the anxiety and depression symptoms of GAD patients, and has a better prognosis for GAD patients.