To observe efficacy and safety of Yangxin Kaiyu tablets on moderate or mild depression. Method: 135 patients were randomized to the tablet arm (n=90, 4 tablets, 3 times per day) and Fluoxetine arm (n=45, 25mg/day in the morning); background medication: 4 Zaoan capsules 30min before bed. Efficacy and safety parameters include the Hamilton depression rating scale (HAMD-17), TCM syndrom scale, Symptom Checklist 90 (SCL-90), self-rating scale for depression (SDS), self-rating scale for Anxiety (SAS), Rating Scale for Side Effects(SERS) and related laboratory analysis at WEEK2 and WEEK6. Results:There were no statistical significance of before treatment (P>0.05). At WEEK2 both groups improved on all parameters (P<0.05); At WEEK6 total effective rate for the tablet was 85.55%. The total effective rate and the scores of various rating scale at the set time points were not statistically different between the two groups. The SAS assessment was better with the tablet. Palpitation, insomnia and the symptom of depression improved significantly in the treatment group and the control group respectively (P<0.05). No safety concerns revealed during the study. Conclusion: the Yangxin Kaiyu tablets can treat moderate or mild depression without obvious safety issue.