Measurement of thymidine phosphorylase (TP) activity in normal liver tissue adjacent to hepatocellular carcinoma (HCC) may predict multicentric recurrence a long time after an operation. The authors investigated this activity in 92 patients with HCC who had a single HCC equal to or less than 5 cm. Fresh samples (tumors with adjacent normal tissues) were collected from 92 patients with HCC who underwent curative hepatic resection. The levels of TP activity in nonfixed, fresh, and frozen HCC specimens with adjacent noncancerous liver tissue were biochemically measured by using an enzyme-linked immunosorbent assay method. Patients who had a high TP level in normal liver tissue had significantly earlier recurrence (median disease-free survival, 819 days; 95% confidence interval [95% CI], 478-1044 days) compared with patients who had a low TP level (median disease-free survival, 1376 days; lower limit of 95% CI, 921 days; P = 0.0171). Multivariate analysis showed that patients who had a low TP level in adjacent liver tissue had a 0.387-fold higher risk of postoperative recurrence compared with patients who had a high TP level (P = 0.0067). TP activity in normal liver tissue adjacent to HCC is related to tumor occurrence and may predict postoperative tumor recurrence.