Abstract: Objective: To detect cyclin E and p21^waf1 proteins quantitatively in oral squamous cell carcinomas(OS-CC), to investigate the correlation between these expression levels and the expression of mutated p53 protein, and to deter-mine the significance of these parameters in tumor differentiation and lymph node metastasis of OSCC. Methods: Flowcytometry was employed to quantitatively detect the expression of cyclin E and p21^waf1 in 8 samples of normal oral epitheli-um and 30 samples of OSCC. The expression of mutated p53 protein was detected by immunohistochemistry. UsingSPSS12.0, we analyzed the correlation between the expression of p21^waf1 and p53 proteins and examined the relationshipbetween these levels and tumor differentiation and lymph node metastasis of OSCC. Results: The expression of cyclin Eprotein in OSCC was higher than that in the normal oral epithelium (t=-6.582,P<0.01), and 63.33%(19/30) of the OSCCpatients presented with upregulated cyclin E. The expression of p21^waf1 protein was lower in OSCC than in the controlgroup (t=8.126,P<0.01), and 53.33%(16/30) of the OSCC patients presented with downregulated p21^waf1. The ratio of cyclinE/p21^waf1 in OSCC was significantly higher than in the normal group (t=-9.434,P<0.01). The expression of p21^waf1 proteinwas lower in OSCC tissues with positive p53 staining than in those without p53 staining (t=3.905,r=-0.491,P<0.01). p21^waf1protein downregulation was significantly associated with lymph node metastasis, while no correlation was found betweencyclin E expression and tumor differentiation or lymph node involvement (P>0.05). Conclusion: OSCC patients have up-regulated cyclin E and downregulated p21^waf1. The downregulation of p21^waf1 protein may partly be a result of p53 mutation,which probably plays a role in lymph node metastasis of OSCC. The imbalance between the positive and negative regula-tors of G1/S caused by cyclin E upregulation and p21^waf1 downregulation might be involved in OSCC.