Objective:To investigate the relationship between oral squamous cell carcinoma (OSCC) and human herpesvirus 6 (HHV-6) infection. Methods:HHV-6 DNA in saliva from patients of OSCC and from health control people was amplified by nest PCR which was HHV-6 specific. Serum anti-HHV-6 IgG titer was tested by anti-HHV-6 IFA kit. HHV-6 glycoprotein B(gB) was detected by immunohistochemistry in OSCC tissues and peritumoral tissues,respectively. Results:The detectable rate of HHV-6 DNA in patients of OSCC is 65.3%,which was much higher than 40% of health control group. But there was no significant difference in clinicopathologic and background variables of OSCC between the PCR positive and PCR negative groups. The geometric mean titer of anti-HHV-6 IgG was significantly higher in the OSCC patients (1∶102.17) than in the health controls (1∶101.50). HHV-6 gB was detected in 6 out of 11 tissues of OSCC and in 3 out of 8 peritumoral tissues. The gB was condensated in tumour cells while was either negative or much lower expression in the intertumor issues. We isolated and cultured tumor cells from one tissue of OSCC which was positive for HHV-6 gB. And then the nude mouse was inoculated with those tumor cells. We could also detected HHV-6 gB in tumor tissues from the mouse. Conclusion:The results demonstrated the frequent presence of HHV-6 in OSCC,although which has no association with clinicopathologic and background variables of patients. An animal model which carry HHV-6 antigen were established and could be useful for understanding the role that the HHV-6 really play in the genesis and treatment of OSCC which is HHV-6 positive.