A systematic review and meta-analysis were conducted to explore the clinical efficacy and coagulation function of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT) in critically ill patients, to provide an effective treatment options for CRRT in severe patients. The English databases Embase, Medline, PubMed, Ovid, Springer, and Web of Science were searched to screen for randomized controlled trials (RCTs) on RCA in the CRRT treatment of critically ill patients published before June 1, 2020. Meta analysis using the RevMan5.3 provided by the Cochrane collaboration network. The search terms included "citrate anticoagulation", "patient in severe condition", "CRRT", "clinical effect", and "coagulation function". ten articles meeting requirements were included, comprising 1,411 subjects. Meta-analysis results showed that after treatment, total calcium/ionized calcium (totCa/ionCa) [mean difference (MD) =0.05; 95% confidence interval (CI): (-0.02 to 0.12); Z=1.31; P=0.19], prothrombin time [MD =4.51; 95% CI: (2.77, 6.24); Z=5.10; P<0.00001], activated partial thromboplastin time [MD =2.56; 95% CI: (1.17, 3.95); Z=3.61; P=0.0003], and thrombin time [MD =4.22; 95% CI: (2.07, 6.36); Z=3.85; P=0.0001] all increased. However, platelet count [MD =-5.75; 95% CI: (-8.85, -2.64); Z=3.63; P=0.0003], cystatin [MD =-0.39; 95% CI: (-0.63, -0.15); Z=3.22; P=0.001], alanine aminotransferase [MD =-17.63; 95% CI: (-20.09, -15.16); Z=14.02; P<0.00001], aspartate aminotransferase [MD =-6.49; 95% CI: (-11.94, -1.04); Z=2.33; P=0.02], creatinine [MD =-3.70; 95% CI: (-5.08, -2.32); Z=5.24; P<0.00001], and total bilirubin [MD =-3.65; 95% CI: (-5.91, -1.40); Z=3.18; P=0.001] all decreased. Except for totCa/ionCa, the differences in other indicators were not statistically significant compared with the control group. RCA can significantly improve the clinical efficacy and blood coagulation indicators of CRRT for severely ill patients.