Introduction: Second-generation anticoagulant rodenticides often cause severe bleeding, which can be life-threatening with limited effective treatment options. This study aimed to evaluate the therapeutic efficacy of hemoperfusion in patients with rodenticide poisoning. Methods: This study conducted a retrospective analysis of 148 patients diagnosed with rodenticide poisoning at the Fifth Medical Center of the Chinese PLA General Hospital between 2014 and 2021. The patients were divided into two groups based on whether they received blood purification treatment. The clinical characteristics, serum drug concentrations, duration of hospital stay, and duration of vitamin K1 (VK1) therapy were compared between the two groups using univariate and multivariate analyses. Subgroup analyses were also conducted to assess the effect of hemoperfusion in patients poisoned with brodifacoum and bromadiolone. Results: This retrospective study included 115 patients hospitalized for rodenticide poisoning. The patients were divided into a hemoperfusion group (24 patients) and a non-hemoperfusion group (91 patients). The hemoperfusion group demonstrated a faster reduction in serum drug concentration. The subgroup analysis revealed that hemoperfusion significantly reduced the duration of VK1 therapy in patients poisoned with brodifacoum (P=0.044). Conclusion: Hemoperfusion effectively reduced serum rodenticide concentrations in patients with poisoning. Moreover, the subgroup analysis suggested that hemoperfusion can reduce the duration of VK1 therapy in patients with brodifacoum poisoning.