Background: In Egypt, bladder cancer (BC) is among the most common cancers. Piwi-interacting RNA associated with bladder cancer (piRABC) expression was downregulated in bladder cancer tissue. The piRABC increase TNFSF4 levels that leads to cancer cell death. This study aimed to assess the roles of piRABC and TNFSF4 in BC detection and to evaluate their roles in cancer grading and staging. Methods: Forty BC patients and 40 controls were enrolled. A quantitative real-time PCR was used to measure the expression of piRABC. ELISA kit was used for determining serum TNFSF4. Results: Compared to controls, BC patients had significantly lower PiRABC expression l and TNFSF4 levels (p<0.0001). With an area under the ROC curve of 0.938 for PiRABC and 0.874 for the TNFSF4, they were able to detect BC. On multivariate analysis, low PiRABC and TNFSF4 levels were significant independent predictive factors of BC (AOR = 133 and 12.4, respectively). With more advanced BC stages, PiRABC expression displayed a negative trend. For BC patients' overall survival, PiRABC and TNFSF4 may be significant independent prognostic factors (p =0.038 and 0.026, respectively). Conclusions: Decreased levels of piRABC expression and TNFSF4 appear to be independent predictors of BC. The low expression of piRABC had accepted prediction criteria for BC better than TNFSF4. The piRABC showed a decreasing trend with tumor grading and staging, while TNFSF4 exhibited a declining tendency throughout BC stages, despite having a small impact in BC grading. Greater expression of TNFSF4 and piRABC was linked to prolonged patient survival rates.