Background: Although cognitive behavioral therapy (CBT) has been known with a theoretical basis for tinnitus patients, there still were lack of clinical evidence. Objective: To evaluate the clinical efficacy of cognitive behavioral therapy (CBT) for treatment of chronic subjective tinnitus. Methods: One hundred patients with chronic subjective tinnitus patients were randomly divided into control (50 cases) and intervention (50 cases) groups, which received the masking therapy and sound treatment and masking therapy and sound treatment plus CBT. The treatment efficacy was evaluated. Results: The total effective rate in intervention group was significantly higher than control group (P < 0.01). After treatment, compared with control group, in intervention group the psychotic somatization, interpersonal sensitivity, depression, anxiety, hostility, terror, and phobic anxiety scores in Symptom Checklist-90 and Tinnitus Handicap Inventory score were significantly decreased (P < 0.05), the serum cortisol level was significantly decreased (P < 0.05), and the serum interleukin-2 level was significantly increased (P < 0.05). Conclusion: Based on the elimination the mood disorders and reduce the stress, CBT can significantly relieve the symptoms of chronic subjective tinnitus.