Objective To study the clinical efficacy of early continuous renal replacement therapy (CRRT) combined with alprostadil in the treatment of hyperlipidemic severe acute pancreatitis (hlsap) and provide theoretical basis for clinical treatment of hlsap. Methods 100 HLSAP patients admitted to Shantou Central Hospital from October 1, 2017 to September 30, 2019 were divided into a treatment group (50 cases) and a control group (50 cases) according to the random number method. The two groups were given severe cases after admission Acute pancreatitis (SAP) who were conventionally treated. On this basis, the control group was given alprostadil treatment, and the treatment group was given early CRRT treatment on the basis of the control group treatment. The clinical efficacy, clinical symptoms and signs relief time of the two groups after treatment are compared. Laboratory indicators, APACHEⅡ score, Ranson score, complication rate, length of hospital stay, treatment cost, fatality rate and recurrence rate. Results The clinical total effective rate of the treatment group was significantly higher than that of the control group (P＜0.05). The remission time of abdominal pain, abdominal distension, nausea and vomiting in the treatment group was significantly earlier than that in the control group (P＜0.001). Before treatment, there was no significant difference in the levels of laboratory indexes (TG, CRP, WBC, Amy, ALT and SCR) between the two groups (P＞0.05). After 72 hours of treatment, the levels of serum TG, CRP, WBC, Amy, ALT and SCR were not significantly different between the two groups (P＞0.05). The levels of TG, CRP, WBC, ALT and SCR in the two groups were significantly lower than those before treatment (P＜0.001), while the levels of Amy were not significantly different between the two groups before and after treatment (P＞0.05). Before treatment, there was no significant difference in Apache Ⅱ score and Ranson score between the two groups (P＞0.05). After 72 hours of treatment, Apache Ⅱ score and Ranson score of the two groups were significantly lower than those before treatment The incidence of complications in the treatment group was significantly lower than that in the control group (P＜0.05). The hospitalization time of the treatment group was significantly shorter than that of the control group, the mortality rate during hospitalization was significantly lower than that of the control group (P＜0.05 or P＜0.001), and the hospitalization expenses of the treatment group were significantly higher than those of the control group (P＜0.001). Both groups were followed up for 1 year after discharge. The recurrence rate of the treatment group was significantly lower than that of the control group(P＜0.05). Conclusion Early CRRT combined with alprostadil in the treatment of hlsap patients can effectively improve the clinical efficacy, promote the remission of symptoms, rapidly reduce the serum triglyceride level, improve laboratory indicators, reduce the incidence of complications, shorten the length of hospital stay and mortality, improve the prognosis of patients, which is worthy of clinical application.