The WAF1/Cip1 protein is an important regulator at the G1 checkpoint in the cell cycle. The WAF1/Cip1 protein binds to the cyclin-dependent kinase complexes and inhibits the kinase activity that is required for cell cycle progression. We investigated the expression of WAF1/Cip1 protein in 14 glioblastoma cell lines and found that WAF1/Cip1 expression was detectable in many of the cell lines, even when mutant p53 was present. We also showed that WAF1/Cip1 protein level was very low in LN-Z308 cells that do not express endogenous p53. Transfection of the wild-type p53 into this cell line activated WAF1/Cip1 expression and inhibited cell growth. In contrast, transfection of the p53 mutant 248Trp failed to activate WAF1/Cip1 expression. Transfection of WAF1/Cip1 alone also inhibited LN-Z308 cell proliferation. However, cotransfection of the p53 mutant 248Trp with WAF1/Cip1 attenuated the growth-suppression effect of WAF1/Cip1. Our analysis with Western blot showed that the levels of cyclin E increased in cells transfected with p53 mutants. We conclude that p53 mutants may counter the negative regulators, such as WAF1/Cip1, by the elevation of positive cell cycle regulators, and the presence of WAF1/Cip1 in tumor cells is not sufficient for growth inhibition.