Objective To explore the clinical significance of continuous renal replacement therapy (CRRT) in the treatment of severe acute pancreatitis (SAP). Methods Retrospective analysis of 64 patients with SAP in our hospital from January 2018 to January 2019 was carried out. The patients were divided into the observation group and the control group according to different treatment regimens, with 32 cases in each group, and the baseline levels of the two groups were consistent. Patients in the control group were treated with conventional medical treatment, and the patients in the observation group were treated with CRRT on the basis of the control group, and the efficacy of the two groups were analyzed and compared. Results The APACHE II scores [(11.02±3.14) vs (13.98±3.27)]、triglyceride[(4.02±1.05) vs (5.62±1.11) mmol/L], C-reactive protein[(88.25±6.73) vs (104.41±10.28) ng/L], procalcitonin[(13.12±4.33) vs (18.55±3.96) ng/mL], blood urea nitrogen[(7.33±1.72) vs (11.24±2.76) mmol/L], serum creatinine[(69.51±15.03)vs(91.12±19.17)mmol/L] of patients in both groups were significantly decreased within 5-7 days after treatment compared with those before treatment, and the decrease of the above indicators in the observation group was significantly greater than that in the control group, P<0.05. The remission time of symptoms[(3.15±1.26) vs (5.22±1.51) d], the stabilization time of signs[(2.52±1.38) vs (4.39±1.50) d], the recovery time of gastrointestinal function[(4.48±1.27) vs (6.21±1.55) d] and the length of ICU stay[(15.03±2.21) vs (18.44±3.27) d] in the observation group were lower than those in the control group, and the analysis of the results was statistically significant (t=5.954, 5.190, 4.884,4.888,all P＜0.05). Conclusions Compared with conventional medical treatment, additional CRRT treatment can significantly improve the inflammatory indicators of SAP, help patients survive from critical state of SAP, which has positive clinical value.