Objective：To investigate the change of circadian rhythm in oral squamous cell carcinoma（OSCC）in vivo. Methods：Totally 32 nude mice were maintained in 12 h light alternating with 12 h dark. Human oral squamous cell carcinoma cell line BcaCD885 was transplanted subcutaneously into nude mice cheeks to develop an OSCC animal model. Mice were sacrificed at 4 different time points 4，10，16，22 h（4 hours after light onset（HALO），10HALO，16HALO，22HALO） of 24 h 3 weeks after transplantation，with 8 mice of each group. Tumors were dissected away and tumor sizes were measured. Tumor cell proliferation index（PI） and apoptosis index（AI） were determined by flow cytometry. Cosine analysis was used to detect circadian rhythm of tumor size，tumor cell PI and AI. Vari－ance of significant difference in the four time groups was tested by ANOVA. Results：Tumor size and tumor cell PI exhibited signifi－cant circadian rhythm. Tumor sizes had significant differences at indifferent time points. Peak and trough values of tumor size appeared at 3.23HALO and 15.23HALO，respectively. Peak and trough values of tumor cell PI appeared at 6.60HALO and 18.16HALO，respec－tively. AI of tumor cells showed no circadian rhythm，but the differences of different time points were significant. Conclusions：Cell proliferation and tumor size of OSCC in vivo show circadian rhythm. Tumor size and AI have significant differences at different time points.