p27^Kip1, a cyclin‐dependent kinase inhibitor, is a negative regulator of the cell cycle, and apoptosis is a genetically encoded program of cell death. To clarify the relationship between the cell cycle and apoptosis, we investigated expression of p27, cyclin D1 and apoptosis‐related proteins (p53, Bax, Bcl‐2 and c‐Myc) in 60 cases of oral and oropharyngeal squamous‐cell carcinoma (SCC) using an immuno‐histochemical approach, and evaluated spontaneous apoptosis in vivo. Our most notable finding was that spontaneous apoptosis in the p27‐positive group was significantly higher than that in the p27‐negative group (p = 0.028). In addition, the percentage of p27‐positive cells was clearly correlated with that of Bax‐positive cells (γ = 0.288, p = 0.028) and with that of cyclin D1‐positive cells (γ = 0.416, p = 0.002). Expression of p27 was inversely associated with the clinical stage of total tumor progression (p = 0.027). However, no correlation was found between p27 expression and the following parameters: gender, tumor size, lymph node metastasis, overall survival and disease‐free survival. Our results give evidence that the action of the cell‐cycle regulator p27 is closely linked with apoptosis in clinical samples from patients and indicate that over‐expression of p27 might induce apoptosis in cancer cells through elevation of Bax expression, thereby acting on tumor progression. Int. J. Cancer (Pred. Oncol.) 84:315–320, 1999. © 1999 Wiley‐Liss, Inc.