The purpose of this study was to investigate the possible association between expression of integrin beta1 and p53 and survival in patients with small-cell lung cancer (SCLC). One hundred four patients with SCLC who had received an initial course of a full-dose of combination chemotherapy between February 1989 and July 1999 were entered in the study. Transbronchial biopsy specimens of tumors obtained before chemotherapy were subjected to immunostaining for integrin beta1 and p53. Twenty-eight and 58 patients could not be evaluated for integrin beta1 and p53 immunostaining, respectively, because the tissue samples had been crushed during the biopsy. Fifty-four patients had tumors with less than or equal to 25% integrin beta1-positive cells and 22 patients had tumors with more than 25% integrin beta1-positive cells, whereas 19 and 27 patients had tumors with less than or equal to 50% and more than 50% p53-positive cells, respectively. By comparison, the overall survival of patients with high expression of integrin beta1 and p53 were significantly worse than those of individuals whose tumors had low expression (log-rank test, p = 0.046 and p = 0.0067, respectively). Moreover, the overall survival of patients with high expression of either integrin beta1 or p53 (n = 42) was significantly worse than that of other patients without high expression of integrin beta1 and p53 (n = 38; log-rank test, p = 0.0003; Wilcoxon test, p = 0.0026). The association between survival and prognostic factors, including gender, age, performance status, clinical stage, and integrin beta1/p53 expression was examined by the Cox proportional hazards model; only integrin beta1/p53 expression was found to be a significant independent factor (hazard ratio = 0.394, p = 0.0005). In conclusion, the high expression of integrin beta1 and p53 in tumor cells is a greater poor prognostic factor than clinical stage in patients with SCLC.