Objective To observe the different expression of NF-κBp65 and cyclinD1 during oral carcinogenesis and to analyze the relationship between the abnormal expression of NF-κBp65, cyclinD1, and the occurrence and development of oral carcinogenesis. Methods The streptavidin-biotin-peroxidase (S-P) immunohistochemical method was employed to detect the expression of NF-κBp65 and cyclinD1 protein in 38 rat tongue carcinogenesis specimens induced by 4-nitroquinoline 1-oxide. Results With the progress of tongue carcinogenesis, the expression of NF-κBp65, cyclinD1 was up-regulated. In normal, mild epithelial dysplasia, moderate epithelial dysplasia, severe epithelial dysplasia, carcinoma in situ and squamous cell carcinoma (SCC), the positive rate of NF-κBp65 was 20%, 20%, 50%, 62.5%, 50% and 83.33%, respectively. There was significant differences between normal and SCC (P<0.05); while the level of cyclinD1 was 20%, 60%, 62.5%, 87.5%, 100% and 83.33%, respectively. There was significant differences between normal and severe epithelial dysplasia, carcinoma in situ and SCC (P<0.01 or P<0.05). There was a significant correlation between the increased levels of NF-κBp65, cyclinD1 and histopathological grade. The positive expression of NF-κBp65 was also associated with cyclinD1 in SCC (r= 0.7353, P<0.05). Conclusion The up-expression of NF-κBp65 and cyclinD1 protein may be correlated to the occurrence and the development of oral carcinoma; activated NF-κB plays an important role in the overexpression of cyclinD1. Furthermore, NF-κB and cyclinD1 may be the useful biomarker of oral precancerous lesion. Objective To observe the different expression of NF-κBp65 and cyclinD1 during oral carcinogenesis and to analyze the relationship between the abnormal expression of NF-κBp65, cyclinD1, and the occurrence and development of oral carcinogenesis. Methods The streptavidin-biotin-peroxidase (SP) immunohistochemical method was employed to detect the expression of NF-κBp65 and cyclinD1 protein in 38 rat tongue carcinogenesis specimens induced by 4-nitroquinoline 1-oxide. Results With the progress of tongue carcinogenesis, the expression of NF-κBp65, cyclinD1 was up-regulated In normal, mild epithelial dysplasia, moderate epithelial dysplasia, severe epithelial dysplasia, carcinoma in situ and squamous cell carcinoma (SCC), the positive rate of NF-κBp65 was 20%, 20%, 50%, 62.5%, 50% and There was significant differences between normal and SCC (P <0.05); while the level of cyclin D1 was 20%, 60%, 62.5%, 87.5%, 100% and 83.33%, respectively. There was significant diffe There was a significant correlation between the increased levels of NF-κBp65, cyclinD1 and histopathological grade. The positive expression of NF-κB p65 was found in both normal and severe epithelial dysplasia, carcinoma in situ and SCC (P <0.01 or P <0.05) also the associated cyclin D1 in SCC (r = 0.7353, P <0.05). Conclusion The up-expression of NF-κB p65 and cyclin D1 protein may be correlated to the occurrence and development of oral carcinoma; activated NF-κB plays an important role in the overexpression of cyclinD1. Furthermore, NF-κB and cyclinD1 may be the useful biomarker of oral precancerous lesion.