Background Non-specific low back pain (NLBP) is a major global socioeconomic burden, and the prevalence of NLBP is still on the rise. At present, there is no ideal cure effect of drugs for this disease. This may be the reason why patients often use complementary therapies. Among them, extracorporeal shock wave therapy (ESWT) has gradually received more attention and has become the main treatment method for NLBP. The purpose of this study is to provide scientific evidence for the effect and safety of meridian theory-based ESWT on NLBP. Objective This study aims to evaluate the effect and safety of meridian theory-based ESWT on NLBP. This study will also provide more high-quality experimental evidence for the clinical application of meridian theory-based ESWT for the treatment of NLBP in the future. Methods This study is a single-blind, multi-center, randomized controlled trial. 64 patients with NLBP, aged 18 to 60 years, will randomly divided into two groups: the experimental group(N.=32), which will receive meridian theory-based ESWT application, and the control group(N.=32) which will receive conventional ESWT treatment. These two applications will be carried out twice a week for two weeks. The primary outcomes will be Visual Analog Scale (VAS) and Oswestry Disability Index (ODI). The secondary outcome will be Surface Electromyography (sEMG). All outcomes will be evaluated at baseline and after the intervention (7 days, 14 days). Discussion The results of this multi-center randomised controlled trial will contribute to providing rigorous clinical evidence for the efficacy and security of meridian theory-based ESWT for NLBP. Trial registration: Chinese Clinical Trial Registry, ChiCTR2100051049. Registered on 10 September 2021, http://www.chictr.org.cn/showproj.aspx?proj=46316