When initiating urate-lowering therapy, using anti-inflammatory prophylaxis therapy for at least 3 to 6 months is strongly recommended. Previous studies have found that zhengqing fengtongning sustained-release tablets (sinomenine) can improve inflammation in the acute phase of gout; however, the efficacy of urate-lowering therapy in reducing frequency of acute flares still needs to be investigated. The aim of the present study is to explore the efficacy and safety of sinomenine for prophylaxis of acute flares when initiating urate-lowering therapy.This randomized, placebo-controlled, double-blinded trial will include a total of 210 gout patients who meet the study criteria. The patients will be randomized (1:1) to the test group and the control group. The intervention is planned to be performed for 12 weeks with a follow-up of 12 weeks. All patients would be administered febuxostat (40 mg/d) and concomitant anti-inflammatory prophylaxis therapy. Sinomenine and colchicine placebo are administered in the sinomenine group, sinomenine placebo and colchicine are administered in the colchicine group. The primary outcome is the rate of acute gout flares in subjects within 12 weeks of the treatment period. The secondary outcomes include the times of acute gout flares and the duration of each acute flares within 12 weeks; the compliance rate in patients whose UA levels ≤6.0 mg/dL (360 μmol/L) at the weekend of 2nd, 4th, 8th, and 12th week in each group; the proportion of patients with ≥1 and ≥2 gout flares within 12 weeks; average visual analogue scale/score pain score during gout flares; and the oral dose of etoricoxib will be used to control the onset of acute flares within 12 weeks.The Institutional Medical Ethics Committee have approved the trial protocol. We plan to publish the results of this study in a peer-reviewed journal.ChiCTR, ChiCTR2100045114, Registered 8 April 2021 http://www.chictr.org.cn/showproj.aspx?proj=124688.Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.