Objective: To evaluate the efficacy and safety of Rupi Sanjie (RPSJ) capsule plus the conventional surgical operation for treatment of hyperplasia nodule of mammary gland. Methods: A meta-analysis was conducted on randomized controlled trials (RCT) related to RPSJ capsule plus surgical operation in the treatment of hyperplasia nodule of mammary gland. The methodological quality of eligible RCTs was assessed according to the criteria from the Cochrane Handbook for Systematic Reviews of Interventions. RevMan5.3 and Stata14.0 were used for data analyses. Trial sequential analysis was performed to estimate the sample size of systematic review base on TSA software v0.9. Results: Twenty-two RCTs were totally included in this study, involving 2135 patients. The result showed the clinical recurrence rate of RPSJ capsule plus surgical treatment group was significantly lower than surgical treatment alone group (RR: 0.25, 95％CI [0.17, 0.37], P<0.01). The clinical cure rate and total effective rate were higher in RPSJ capsule plus surgical treatment group than the conventional surgical treatment group (RR: 1.63, 95％CI [1.46, 1.82], P<0.01); (RR: 1.29, 95％CI [1.22, 1.37], P<0.01). Application of RPSJ capsule decreased the occurrence of adverse events including nausea, vomiting, irregular menstruation, constipation, dizziness, and headache etc. (RR: 0.90, 95％CI [0.54, 1.49], P=0.68). The results of trial sequential analysis demonstrated that the current available data did not reach the expected value. Conclusion: RPSJ capsule plus the conventional surgical treatment was more effective in reducing the clinical recurrence rate, and improving the total clinical effective rate and clinical cure rate, with a decrease in the occurrence of adverse events.