Abstract: The FHIT gene alterations may occur as early consequences for the urinary bladder cancer. The present study aimed to identify and analyze the role of homozygous deletion (HZD) and transcriptional alterations of fragile histidine triad (FHIT) gene in the development and progression of bilharzial bladder cancer in Egyptian patients. The possible associations between FHIT abnormalities and some clinical variables that have prognostic impact in bilharzial bladder cancer patients were determined. In addition, the relations between homozygous deletion (HZD) of FHIT gene, FHIT protein, p21WAF1 expression and apoptosis were demonstrated. We investigated 42 human bladder cancer and 10 normal adjacent tissues as a control group. HZD of the FHIT gene, FHIT protein, p21 protein and apoptosis were assessed by PCR, immunohistochemistry and DNA ladder method, respectively. FHIT HZD deletions have expressed a significant correlation with FHIT protein (p≤0.04), p21WAFI protein expression (p≤0.005) and apoptosis (p≤0.03). On the other side, no correlations were detected between FHIT homozygous deletions and tumor type, tumor grade and gender. Therefore, the FHIT gene deletions could be important in the development and/or progression of urinary bladder cancers and may be used as an independent prognostic indicator for the clinical outcome in patients with these tumors.