It is difficult to evaluate surgical stress of patients with hepatocellular carcinoma (HCC). Cytokine production from the liver is decreased due to the liver dysfunction that is usually associated with HCCs. Therefore, we evaluated surgical stress after hepatectomy by measuring intracellular cytokines of lymphocytes in peripheral blood. We examined 22 patients with digestive cancers (8 with HCC, 10 with gastric cancer, and 4 with esophageal cancer). The concentrations of serum IL-6 levels 6 h after hepatectomy, gastrectomy, and esophagectomy were 268 +/- 84, 309 +/- 93, and 1,323 +/- 364 pg/ml, respectively. There was no significant difference between hepatectomy and gastrectomy, though based on clinical observations, it is estimated the surgical stress of hepatectomy was greater than that of gastrectomy. Conversely, the percentage of CD4+IL-6+ cells 6 h after surgery was 8.5 +/- 2.8, 3.3 +/- 0.6, and 7.8 +/- 3.4%, respectively. The percentage of CD4+IL-6+ cells after hepatectomy was significantly higher than that after gastrectomy. We estimated that the percentage of CD4+IL-6+ cells was an appropriate indicator of surgical stress on HCC, because the percentage of CD4+IL-6+ cells correlated well with the duration of surgery more than did the serum IL-6 levels. These results suggest that the percentage of CD4+IL-6+ cells may help in accurately evaluating surgical stress in patients with liver dysfunctions such as HCC.