Abstract: Objective To investigate the effect of celecoxib on regulatory T cells (Treg) in mouse hepatocellular carcinoma (HCC). Methods Total of 40 mice was divided into two subgroups, normal animal groups include control and celecoxib group, HCC groups include control and celecoxib group. 30 mg/kg of celecoxib were given daily for 24 days for celecoxib groups. All mice were sacrificed after 24 days treatment and the removed tumor weight were measured. By detecting CD4 and CD25 with flow cytometry, the level of Treg in peripheral blood was determined. The expressions of Forkhead/winged helix transcription factor-3 (Foxp3) protein in the tumor infiltrating lymphocytes (TILs) and cyclooxygenase-2(COX-2) protein in tumor tissue were measured by immunohistochemistry techniques. Results The mean weight of tumor in celecoxib group is much lower than that of control group (0.82±0.30) g vs. (1.41±0.63) g, P<0.05. The percentage of Treg in total CD4⁺T cells isolated from the peripheral blood of HCC animals in control group was higher than that of normal control group (4.26±0.89)% vs. (3.01±0.65)%, P<0.05. After treatment with celecoxib, the percentage of Treg was decreased (3.04±0.74)% vs. (4.26±0.89)%, P<0.05 and the percentage of Foxp3 positive cell in TILs was also decreased (8.87±3.72)% vs. (30.78±9.26)%, P<0.05. The tumor tissue COX-2 protein expression in celecoxib group was lower than in that of control group IOD (2.90±1.030) vs. (6.63±2.279), P<0.01) and the changing of COX-2 in tumor tissue was according to Treg in the peripheral blood. Conclusion Treg cells are increased in the peripheral blood of HCC mice and COX-2 inhibitor could decrease the percentage of Treg cell in the peripheral blood or TILs.