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To evaluate the clinical significance of preoperative serum levels of interleukin-10 (IL-10) and interleukin-6 (IL-6) in patients with resectable hepatocellular carcinoma (HCC).IL-10 is an immunosuppressive factor and IL-6 is a multifunctional cytokine that plays a role in host defense mechanisms. Both have been reported to be related to the disease prognosis in some human solid tumors. Their role in human HCC has not been investigated.Preoperative serum samples of 67 patients with HCC who underwent potentially curative resection and 27 normal healthy donors were assayed. Levels of IL-10 and IL-6 were determined by enzyme-linked immunosorbent assay. The clinical significance of serum IL-10 and IL-6 was evaluated and compared with conventional clinicopathologic factors.Levels of IL-10 and IL-6 were significantly higher in patients with HCC than in healthy subjects. There was no correlation between IL-10 and IL-6 levels. Tumor resection resulted in a decrease in IL-10 and IL-6 levels. On univariate analysis, patients with high IL-10 levels had a worse disease-free survival, but IL-6 levels had no correlation with the disease-free survival. Multivariate analysis identified IL-10 levels as a predictor of postresectional outcome, in addition to the well-established clinical risk factors.In patients with HCC, the preoperative serum IL-10 level is related to the clinical outcome. IL-10 may play an important role in the progression of HCC.