The goal of this study was to investigate the relationship among immunohistochemical expression of epithelial growth factor receptor (EGFR) family proteins, p21, p27 and prognosis in patients with high-grade astrocytoma. Expression of EGFR family proteins (c-erbB-1, c-erbB-2, c-erbB-3, c-erbB-4), p21 and p27 and Ki-67 labeling index (LI) were studied in 59 samples of high-grade astrocytoma. Expression of protein levels was analyzed by immunohistochemical staining of formalin-fixed and paraffin-embedded sections. Results were analyzed in relation to age, gender and survival. Overexpression of c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4 was found in 40 (67.8%), 17 (28.8%), 3 (5.1 %) and 42 (75.0%) samples, respectively. Similarly, low expression of p21 and p27 was observed in 50 (84.8%) and 27 (45.8%) samples. Mean Ki-67 LI was 17.3 ± 1.1. Cox multiple regression analysis showed that c-erbB-1 (Hazard rate(HR) 1.57, 95% Confidence interval (Cl) 1.08-2.36; p=0.017), c-erbB-4 (HR 1.79, 95%CI 1.20- 2. 7 4; p=0.004) and p27 (HR 0.50, 95%CI 0.30-0.82; p=0.006) were significantly associated with survival. High expression of c-erbB-1 and c-erbB-4 and low expression of p27 were associated with poor prognosis in these patients.