Aims and Background In several neoplastic diseases including hepatocellular carcinoma (HCC) immunosuppression is correlated with disease stage, progression and outcome. Moreover, recent studies have demonstrated that cyclooxygenase-2 (COX-2) enhances tumor growth in HCCs. The present study analyzed the correlation between local immune responses and COX-2 gene expression levels in patients with primary HCCs. Methods Fresh tissues were obtained from 59 patients who underwent resection of an HCC. The COX-2 gene expression levels were quantified by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and compared with the CD8+ T cell densities detected by immunohistochemistry. Results COX-2 gene expression was detected in 35 of the 59 tumors. The CD8+ T cell density in COX-2-expressing tumors (6.1 cells/high-power field (HPF), x200 magnification) was suppressed compared with that in non-COX-2-expressing tumors (13.6 cells/HPF, P = 0.009). Tumor COX-2 gene expression was associated with a poorer disease-free survival rate. Conclusions Elevation of the tumor COX-2 level is correlated with the suppression of local immune responses in HCCs, suggesting that COX-2 plays a role in early tumor recurrence in the residual liver in patients after HCC resection.