BACKGROUND: With the changes in lifestyle and diet, the incidence and mortality of colorectal cancer (CRC) is increasing in China. CRC mainly develops from colorectal adenomas (CRAs). There is a lack of chemopreventative drugs with definite efficacy for CRAs. Tiaochang Xiaoliu Decoction (TXD) was developed by Professor Yunjian Luo and has been used clinically over the last ten years for the prevention of CRA recurrence. To facilitate its clinical use, TXD was further standardized and produced as "Tiaochang Xiaoliu Decoction Granules (TXDG)". A study was designed to investigate the preventive effects of TXDG on the recurrence of CRA. METHODS: A randomized, double-blinded, controlled, and multi-center experiment is proposed to assess the effectiveness and safety of TXDG. Patients with CRAs (after complete polypectomy under colonoscopy) will be randomly divided into two groups, one will be treated with TXDG (the TXDG group) and the other will be treated with a TXDG mimetic agent (the TXDG mimetic group). The patients will be treated for 6 months and followed up for 3 years. Follow-up colonoscopy is expected to be carried out within 1 to 3 years after the baseline examinations. The primary outcome measure is adenoma detection rate within 1 to 3 years. The secondary outcome measures are the number, location, and pathology of the adenomas, and the polyp detection rate. DISCUSSION: Reliable objective evidence will be provided to evaluate the efficacy and safety of TXDG as an accessorial therapy for CRA occurrence in post-polypectomy patients. TRIAL REGISTRATION: ChiCTR2000035257.