Objective To compare the effects of cognitive-behavior therapy (CBT) and domestic paroxetine in the treatment of minor depression. Methods A therapeutic technique model for the treatment of minor depression was established. Sixty-four patients with minor depression meeting DSM-IV criteria were divided into CBT and paroxetine groups with 32 patients respectively, and were treated for six weeks. The Hamilton Depression Scale (HAMD) was used to evaluate the clinical efficacy and relapse/recrudescence rate of the two groups. Side effects of paroxetine were also recorded. Results At the end of 2 weeks, no significant difference was noted in the reduction of the HAMD score between the two groups. At the end of 6 weeks, there was little difference in thHAMD score reduction between the two groups (F=8.3,P= 0). No significant difference was found in the curative effects between the two groups (u=316.5,P=0.06).In the paroxetine group, cure rate was 20.7%, significant improvement rate was 48.3%; In the CBT group, cure rate was 10.0%, significant improvement rate was 36.7%.The relapse/recrudescence rate after six in the paroxetine group was higher than in cognitive-behavior therapy group at 6 months’ follow-up (u=106.5,P=0.04).Conclusion The clinical efficacy of cognitive-behavior therapy for minor depression seems to be similar to that of paroxetine. The established model of CBT can be used in clinical practice.