AIM: The pre-prescription system of outpatient was established and implemented based on six sigma DMAIC model to ensure the safety of drug use and promote rational of drug use. METHODS: The rules database was made scientifically and precisely, according to DMAIC model of Six Sigma--define, measure, analyze, improve and control. The pre-prescription system of our hospital was established and improved,through adopting the prescription review mode of interception and Intervention.And the process management was continued to optimize. RESULTS: The rule-making of pre-trial system for outpatient prescription in our hospital was reasonable, and the rate of clinical approval and acceptance was high. After the system audit, the average rate of doctor's revision was 76.32%, and the average rate of Pharmacist's intervention was 63.23%, the effective rate and qualified rate of pharmacist intervention were 97.23% and 96.87%, respectively. CONCLUSION: Based on Six Sigma DMAIC model, the pre-trial system for outpatient prescription was established and implemented, which improved the level of rational drug use, effectively ensured the safety of drug use, and improved the satisfaction of patients.