Recently, the p53R2 gene has been isolated and shown to play a crucial role in DNA repair after DNA damage. The p53R2 gene encodes the p53 inducible ribonucleotide reductase small subunit 2 homologue, which is part of the p53 pathway. However, the function of p53R2 in human cancer is still unclear. We investigated p53R2 mRNA expression in human oral normal epithelium, epithelial dysplasias and squamous cell carcinomas (SCCs). Surgical or biopsy-proven specimens of 10 normal epithelium, 48 epithelial dysplasias and 63 SCCs were collected in our department. Then, p53R2 was identified by in situ hybridization to visualize and localize the expression of specific mRNAs. The authors examined the p53 gene mutation by polymerase chain reaction-single strand conformation polymorphism analysis. p53, mdm2, p21(WAF1/CIP1) and Ki-67 expression was detected by immunohistochemistry. p53R2 expression was detected in none of ten normal epithelium (0%), ten of 48 dysplasias (20.8%) and 33 of 63 SCCs (52.4%). In oral SCC, the expression of p53R2 was significantly associated with tumor size, lymph node metastasis and histological differentiation (P=0.014, 0.046 and 0.022, respectively). p53R2 expression was significantly associated with p53 abnormality in epithelial dysplasia and SCC (P=0.034 and 0.009, respectively). Of 63 patients, 37 received preoperative radiochemotherapy. p53R2 mRNA expression was significantly associated with the pathologic response to radiochemotherapy (P=0.031). This study suggested that p53R2 expression could be associated with oral carcinogenesis. The presence of p53R2 mRNA expression would be a predictive factor for tumor development, tumor cell differentiation and the sensitivity to radiochemotherapy in oral SCC.