Background: Anemia is one of the main complications of chronic kidney disease especially end-stage renal disease, which includes treatment with erythropoiesis-stimulating agents and ferralia, including intravenous and oral iron. However, intravenous iron may pose limitations, such as potential and lethal infusion reactions. Oral iron is mainly composed of divalent iron, which can excessively stimulate the gastrointestinal tract. Iron polysaccharide complex capsules (PIC) is a novel oral iron trivalent supplement with higher iron content and lower gastrointestinal irritation. However, since high-quality evidence-based medicinal support is lacking, it is necessary to conduct clinical studies to further evaluate the effectiveness and safety of oral PIC in chronic kidney disease patients. Methods: This randomized controlled trial uses an open-label, parallel group design, where the efficacy and safety of maintenance hemodialysis (MHD) patients is evaluated. The experimental group is assigned a conventional drug treatment and PIC and the control group is assigned a conventional drug treatment and sucrose iron injection. The primary endpoint is transferrin saturation (TSAT). Secondary endpoints include hemoglobin (Hb) concentration, hematocrit (Hct), hypersensitive C-reactive protein (HsCRP), pharmacoeconomic evaluation, quality of life, etc. The treatment will last for 24 weeks with follow-up visit at baseline (within 7 days prior to initial treatment) and weeks 4, 8, 12, 16, 20, and 24 after initial treatment. Leading unit of this clinical research is Renji Hospital, School of Medicine, Shanghai Jiao Tong University; 8 well-known hemodialysis centers in Mainland China are included in this study with 186 patients selected through competitive enrollment. Discussion: It is expected that it will provide strong evidence to reveal the clinical efficacy and safety of oral iron in the treatment of chronic renal anemia in MHD patients through this clinical trial.Trial registration: This study has been registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) on March 23rd, 2020. Trial registration number is ChiCTR2000031166.