Abstract： Objective To analyze risk factors in order to predict the in-hospital mortality of patients with se-vere acute pancreatitis (SAP), especially the factor of total cholesterol. Method Factors for predicting in-hospi-tal mortality were evaluated retrospectively from the clinical data collected from 338 SAP patients of Tianjin Nankai Hospital between January 1999 and December 2008 according to the Guidelines for for clinical diagnosis and classi-fication of Acute Panereatitis set by the Society of Chinese Medical Association in 2003. The patients were treated with intensive care, blood routine examination, blood biochemical test and even computed tomography within 24 hours after admission. The patients were divided as per outcome into deceased and survivor group. All patients were admitted within 72 hours after the onset of symptoms. The Off-square test was used for univariate analysis and multivariate test was performed by logistic regression. Results Compared with TC≤3.67 mmol/L, when the TC was between 3.67 -4.37 mmol/L, OR was 0.664 (P = 0.412), while TC was between 4.37 mmol/L and 5.23 mmol/L, OR was 0.144 (P =0.021).The OR was 1.013 (P =0.018) when TC was ≥5.23 mmol/L. The variation of serum TC levels was accompanied with the changes of C-reactive protein (CRP). When the CRP was ≥170 mg/L, OR was 7.074 (P =0.031). When the serum ALB≤30 g/L, OR was 7.224 (P =0.029).Conclusions The CRP, ALB, TC can be used for early predicting the in-hospital mortality of SAP patients. TC is a protective factor when it was between 4.37 mmol/L and 5.23 mmol/L, while it is a risk factor when ≥5.23 mmol/L or≤3.67 mmol/L. CRP> 170 mg/L or ALB < 30 g/L increases the probability of fatal outcome. Low level of albumin is a stronger predictor than the high level of CRP. Moderate elevation of TC level seems to in-crease the resistance to inflammation and hence improving the survival rate of patients with SAP and reducing the in-hospital mortality.