Objective: To observe the clinical efficacy and adverse reactions of Paroxetine combined with electro-acupuncture (EA) in treating depression. Methods: Forty-two patients with depression were randomly assigned to the observation group (22 patients) treated with EA combined with Paroxetine, and the control group (20 patients) treated with Paroxetine alone, and the therapeutic course for both groups was 6 weeks. The therapeutic efficacy and adverse reactions were evaluated with scores by Hamilton depression scale (HAMD) and treatment emergent symptoms scale (TESS),respectively. Results: HAMD scores determined at the end of the 1st, 2nd, 4th, and 6th week of the treatment course were significantly lower in the observation group than those in the control group (P＜0.05). The significant improvement rate evaluated at the end of the 6-week treatment was remarkably higher in the observation group than that in the control group (72.7% vs 40.0%). No significant difference of TESS scores was found between the two groups. Conclusion: EA combined with Paroxetine has better clinical efficacy than that of Paroxetine alone, with milder adverse reaction and quicker initiation of effect.