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Preoperative serum lactate dehydrogenase (LDH) has been used as a prognostic indicator for patients with hepatocellular carcinoma (HCC) treated with sorafenib or undergoing transcatheter arterial chemoembolization, but its significance in predicting survival of HCC patients who received curative resection remains undefined. A total of 683 patients with histopathologically confirmed HCC were enrolled in this study. The prognostic significance of preoperative serum LDH was determined by Kaplan-Meier analysis and a Cox proportional hazards regression model. The association between the preoperative serum LDH and clinicopathological parameters was evaluated by the χ(2) test or linear regression analysis when appropriate. Higher preoperative serum LDH level was associated with worse prognosis. In a multivariate Cox proportional hazards analysis, the preoperative serum LDH level could predict overall survival and recurrence independently. Higher preoperative serum LDH level is associated with the elevated serum alpha-fetoprotein, the presence of hepatitis B surface antigen, larger tumor size, the presence of macrovascular invasion, the advanced tumor-lymph node-metastasis stage, worse tumor differentiation, and Child-Pugh B. Preoperative serum LDH level was an inexpensive, simple, convenient, and routinely measured biomarker exhibiting a potential to select patients at high risk with poor clinical outcome for appropriate treatment strategies.