The link between p53 as a prognostic marker and O2-free radicals as an aetiological factor for cancer bladder needs to be clarified. The current work was therefore, carried on 50 male subjects. Their ages were ranged from 38-80 years with the mean value 56.3 . They were 40 patients with cancer bladder in different grades compared with 10 health male subjects as controls. Our patients were classified histopathologically into 4 groups. Each group comprised 10 patients. Venous blood samples were taken from all patients , pre-operatively and another samples were taken after 21 days , post operatively. Also tissue biopsies with safety margins were taken for determination of malondialdehyde (MDA) and p53 protein. The results of this work showed that; pre-operative and post operative serum MDA and p53 were significantly increased in all grades compared with the control group (p<O.O5) except post operative serum MDA in grade III which showed non-significant difference .Comparative study of post operative serum MDA and p53 versus pre-operative, the data showed statistical significant decrease (p1<O.O5). However, tissue biopsies homogenates showed that MDA was significantly decreased in grade III and grade IV (p<O.O5) but non-significant in grade I and grade II while p53 was significantly increased in all grades when compared with those obtained from healthy tissues. Correlation study ; showed that ; preoperative serum MDA had a significant positive correlation with serum p53 in all grades of cancer (p<O.O5). Meanwhile, tissue MDA had a significant positive correlation with tissue P53 in grade IV (p<O.O5). We could conclude that; , free radicals, lipid peroxidation and over expression of P53 were inter-related to each others. However, oxy radicals cause genetic changes of P53 resulting in loss of programmed cell death (apoptosis) which play a critical role in tumorgenesis. The rapid decline of serum p53 after radical cystectomy seemed to be a useful prognostic marker for follow up of patients with cancer bladder.