Objective: To investigate the efficacy and safety of namorestat mesylate (NM) in maintenance hemodialysis (MHD) in patients with chronic renal failure (CRF). Methods: 88 patients with CRF who were treated with MHD in the nephrology department of our hospital from August 2023 to August 2024 were selected as subjects. The patients were divided into control group and study group by random number table method, with 44 cases in each group. The control group was treated with anticoagulation of low molecular weight heparin sodium in MHD treatment. The study group applied NM anticoagulation in the treatment of MHD. Anticoagulation effect, blood clotting function [platelet (PLT), activated clotting time (ACT), prothrombin time (PT) activated partial thromboplastin time (APTT), fibrinogen (FIB)], renal function [Serum creatinine, SCr), Blood urea nitrogen (BUN) level] and adverse reactions of the two groups were analyzed and compared. Results: There was no significant difference in anticoagulation effect between the two groups (P>0.05). Before treatment, there were no significant differences in ACT, APTT, PT, FIB and PLT between the two groups (P>0.05). After treatment, there were no significant differences in ACT, PLT and FIB between the two groups compared with before treatment (P>0.05), but PT in both groups was significantly decreased compared with before treatment (P<0.05). After treatment, APTT and PT in the study group were significantly shorter than those in the control group (P<0.05). After treatment, the SCr and BUN levels in both groups were significantly lower than before treatment, and the SCr and BUN levels in the study group were significantly lower than those in the control group (P<0.05). The incidence of adverse reactions in study group was significantly lower than that in control group (P<0.05). Conclusion: The anticoagulation effect of NM in the treatment of MHD is similar to that of low molecular weight heparin sodium, but NM anticoagulation can improve the coagulation function and renal function of patients, and reduce adverse reactions.