To evaluate the clinical effect and safety of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) after hepatectomy. A retrospective analysis of the clinical data of all patients with AKI after hepatectomy for CRRT admitted to surgical intensive care unit (ICU) of the First Affiliated Hospital of Xi'an Jiaotong University from January 19th, 2013 to January 19th, 2018 was performed. According to the different anticoagulants, the patients were divided into no anticoagulant group (NA group), low molecular heparin anticoagulation (LMHA) group and RCA group. The general data of patients during the perioperative period; renal function, the internal environment, electrolyte and blood coagulation function before and after CRRT; the filter time, the number of filters and adverse events (bleeding, frequent filter blood coagulation, metabolic alkalosis, metabolic acidosis, hypocalcemia, citrate accumulation, etc.) during CRRT were collected. Kaplan-Meier survival curve was used to analyze the life span of the first filter during different anticoagulation. A total of 67 cases were included in this study, including 11 in the NA group, 25 in the LMHA group and 31 in the RCA group. There was no significant difference in gender, age, underlying disease, etiology (tumor), Child-Pugh stage (A or B), CT angiography (CTA), basic renal function [serum creatinine (SCr), cystatin C (Cys C)], the American Society of Anesthesiologists (ASA) stage; surgical approach; intraoperative bleeding volume, blood transfusion, blood pressure, time of duration of low blood pressure; and postoperative circulatory failure, hepatic insufficiency and sepsis among three groups. However, the length of ICU stay in RCA group was significantly less than the LMHA group and NA group (days: 8.16±2.24 vs. 10.48±5.11, 13.29±6.64, both P < 0.05). Compared with before CRRT, the levels of SCr, Cys C and Lac were significantly decreased in RCA group and LMHA group after CRRT [SCr (μmol/L): 89.02±21.90 vs. 248.30±55.32, 105.10±49.00 vs. 270.10±156.00; Cys C (mg/L): 2.18±0.95 vs. 2.94±1.26, 2.26±0.76 vs. 3.07±0.90; Lac (mmol/L): 2.21±1.46 vs. 3.62±1.73, 2.37±1.24 vs. 4.03±1.69, all P < 0.05]; in addition, LMHA group and NA group had significant effects on hemoglobin (Hb), platelet count (PLT) and activated partial thromboplastin time (APTT) after CRRT [Hb (g/L): 85.4±5.1 vs. 99.6±23.6, 80.0±7.6 vs. 101.4±7.8; PLT (×109/L): 27.60±8.22 vs. 62.04±16.49, 21.36±3.91 vs. 61.45±17.69; APTT (s): 63.07±10.25 vs. 41.52±3.65, 49.56±5.77 vs. 41.09±3.45, all P < 0.05]; at the same time, Cys C level and prothrombin time (PT) in the NA group after CRRT treatment were significantly increased compared with the others [Cys C (mg/L): 3.59±0.64 vs. 2.29±0.51, PT (s): 26.41±2.43 vs. 23.64±1.92 , both P < 0.05]. Finally, the time of filters (hours: 60.52±8.82, 31.04±7.03, 13.73±6.26, F = 183.412, P < 0.001) and the number of filter during treatment (number: 2.03±0.60, 3.12±0.73, 4.64±1.29, F = 45.933, P < 0.001) in the RCA group, LMHA group and NA group had statistically significant difference. Meanwhile, the incidence of adverse events such as bleeding (0 vs. 4, 7, χ 2 = 23.961, P < 0.001) and frequent filter coagulation (1 vs. 10, 11, χ 2 = 35.413, P < 0.001) in RCA group was significantly lower than that in LMHA group and NA group. Kaplan-Meier survival analysis showed that the life time of the first filter in RCA group was significantly longer than that in LMHA group and NA group (χ2 = 139.45, P < 0.05). The application of RCA in patients with AKI after hepatectomy during CRRT is safe and effective, which can significantly prolong the life of the filter and reduce the risk of bleeding.