Severe acute pancreatitis (SAP) is a serious systemic disease with high mortality. Ulinastatin is a drug widely used for patients with SAP and multiple organ failure syndrome. The present study aimed to investigate the capacity of the serum C-reactive protein (CRP) levels to predict the therapeutic effects of ulinastatin combined with somatostatin as well as determine the severity of SAP. SAP patients were treated with ulinastatin combined with somatostatin and serum CRP levels were measured. The computed tomography severity index (CTSI), acute physiology and chronic health evaluation II (APACHE II) and gastrointestinal failure scores were used to determine the therapeutic effects. All patients were assigned to the effective group and the ineffective group. Receiver operating characteristic curve analysis was performed to determine the sensitivity and specificity of CRP levels in predicting the severity of SAP and patient prognosis. Logistic regression analysis was adopted to investigate the factors influencing the therapeutic effects. Prior to and after treatment, serum CRP levels in patients of the effective and ineffective groups were significantly different. After treatment, serum CRP levels in patients of the effective group exhibited a more obvious reduction. The sensitivity and specificity of serum CRP levels in predicting the therapeutic effects of ulinastatin combined with somatostatin in SAP patients upon hospital admission were 0.813 and 0.934, respectively. Serum CRP levels were positively correlated with APACHE II, CTSI and gastrointestinal failure scores of SAP patients. The logistic regression demonstrated that serum albumin, creatinine and CRP levels on admission were factors influencing the therapeutic effects of ulinastatin combined with somatostatin in SAP patients. These results indicate that serum CRP levels may have a predictive value regarding the therapeutic effects of ulinastatin combined with somatostatin and are an indicator of the severity of gastrointestinal failure in SAP.