OBJECTIVE Acute renal failure (ARF) is one of the most common causes of death in patients with severe acute pancreatitis (SAP). Here, we aimed to investigate the risk factors of ARF in patients with SAP, assess the prognosis of patients with SAP and ARF, and seek potential measures to prevent ARF. METHODS A cross-sectional study was performed to analyze the data from patients with SAP. Both univariate and multivariate logistic regression analyses were performed, including 15 indices such as age, history of renal disease, Acute Physiology and Chronic Health Evaluation II scores, hypoxemia, abdominal compartment syndrome (ACS), and others. Univariate analysis was also used to compare the prognosis between the groups of patients with SAP with and without ARF. RESULTS There was a significant difference in age, history of renal disease, Acute Physiology and Chronic Health Evaluation II scores, hypoxemia, and ACS between the groups with and without ARF. Patients with SAP and ARF had significantly longer average length of stay and intensive care unit length of stay and higher infection rate of the pancreas and mortality rate. CONCLUSIONS The significant risk factors for ARF in patients with SAP include history of renal disease, hypoxemia, and ACS. Measures that can prevent ARF include homeostasis maintenance, adequate perfusion of the kidneys, adequate oxygenation, and abdominal decompression to avoid ACS.