The expression and clinicopathological significance of Quox-1 gene was studied in oral squamous cell carcinoma (OSCC). Immunocytochemistry and western blot analysis were used to examine the different expressions of Quox-1 protein in 114 OSCC specimens, 34 oral epithelial dysplasia specimens, and 16 normal oral mucosa specimens. RT-PCR and virtual Northern Blot were also used to examine the expression of Quox-1 mRNA. It was found that Quox-1 was not expressed in normal epithelium. However, as dysplastic lesions progressed Quox-1 expression increased (p < 0.01), and Quox-1 expression was not significantly different between severe dysplasia and highly differentiated OSCCs (p > 0.05). As the degree of differentiation decreased, Quox-1 positivity increased in OSCC (p < 0.01), and the rate of Quox-1 (81.58%) positivity in OSCC was higher than that in normal oral mucosa (p < 0.01). Our findings imply that the positive expression of Quox-1 is correlated with the histological classification of OSCCs. Thus, the expression of Quox-1 in OSCC may serve as a significant predicting factor of proliferative status and malignant degree, and it may also be a biological detection marker of oral mucosas initial cancer and of OSCC.