Transitional cell carcinoma (TCC) of the bladder remains a significant health problem worldwide. The molecular mechanisms of tumor development and progression are complicated but likely involve the interaction of tumor suppressor genes, oncogenes, cell cycle regulatory proteins and other factors. Hence this study tries to explore the role of p53, bcl-2, c-myc, Ki-67 and nuclear factor-kB (NF-kB) in TCC of the bladder in correlation with different clinicopathological criteria which are tumor grade, muscle invasion by the tumor, schistosomiasis and presentation whether primary or recurrent tumor. Thirty patients with TCC of the bladder were included and were diagnosed by histopathology. The expressions of the previously mentioned genes were studied by immunohistochemistry (1HC). while the transcription factor NF-kB was studied by in situ hybridization technique. Moreover the cell-mediated immunity of the patients was studied by the MTT assay in response to PHA and Schistosoma egg antigen (SEAg) as mitogens. Results showed that there was a state of immunosuppression in all patients may be aggravated by schistosomiasis. The results of p53 and bcl-2 were correlated with tumor grade, muscle invasion and schistosomiasis significantly (p<0.05), but not correlated with tumor presentation. C-myc expression was significantly (p<0.05) correlated with muscle invasion only, while Ki-67 wa^ correlated with tumor grade, muscle invasion and tumor presentation but not with schistosomiasis. The correlation between these cell cycle proteins was generally good except that between bcl-2 and p53, which was moderate and between bcl-2 and c-myc was poor. The results of in situ hybridization of NF-kB showed there was a significant correlation (p<0.05) with muscle invasion and schistosomiasis but not with other criteria. Moreover, the associations of NF-kB with the cell cycle proteins were significant (p<0.05) regarding the clinicopathological criteria, but there was no significance between tumor grade and either c-myc or Ki-67. The current study showed the possible role of each of tumor suppressor protein (p53), the oncoprotein (c-myc), cell cycle regulatory-protein (bcl-2), the proliferative antigen (Ki-67) and the transcription factor (NF-kB) in TCC of the bladder through their complex interaction with each other.