Few Data are available regarding expression of proliferating cell nuclear antigen (PCNA) versus overexpression of p 53 protein and prognosis for oral squamous cell carcinoma (O-SCC). This study evaluated the relationship between expression of PCNA and p 53 protein and certain clinical and pathologic parameters to prognosis in O-SCC. Scattered PCNA immunoreactive cells were found in 50 of 51 (98.0%) tumors. The mean PCNA-labelling index (PCNA-LI) of O-SCC was 34.7 +/- 12.0% (n = 50). The PCNA-LI was significantly high in O-SCC when compared to normal squamous epithelium (3.9 +/- 2.1%, n = 10). Altogether, 28 of 51 (54.9%) tumors showed nuclear immunoreactive for the p 53 protein. p 53-positive nuclei were clearly stained as granular or reticular in O-SCC. Microscopically, it appeared that the staining patterns of PCNA- and p 53-positive cells were quite similar. The mean value of PCNA-LI for the p 53-positive cases was 37.9 +/- 11.9% (n = 28), which was significantly higher than the 30.8 +/- 11.1% of the 23 negative cases. The survival rates at 3-year and 5-year for patients with p 53-negative O-SCC were 78.3% and 73.4%, respectively, while those for patients with p 53-positive O-SCC were 51.9% and 43.2%, respectively. No significant correlation could be found between PCNA-LI and T classification, N classification and Stage classification. The expression of p 53 was detected in 48.5% (16/33) of cases without regional lymph node metastasis, and 66.7% (12/18) with regional lymph node metastasis. There was a significant difference between PCNA-LI and p 53-positive cases, and prognosis. In PCNA-LI, the Grade 4 by mode of invasion was significantly higher than Grade 1, 2 and 3. The PCNA-LI and p 53-positive cases were significantly correlated with histological grading of malignancy. The present study shows a relationship between PCNA and p 53 protein. It also suggests that both PCNA and p 53 positive rates are the malignant potential of the O-SCC.