Abstract BACKGROUND: Despite advances in intravesical therapy and surgery, up to 30% of NMIBC suffer progression to MIBC. OBJECTIVES: To identify the valuable prognostic biomarkers, we analyzed the immunohistochemical expression of Sox2, YAP1, and IMP3 in 60 cases of NMIBC who underwent TURBT with adjuvant intravesical bacillus-Calmette-Guerin (BCG). METHODS: The immunohistochemical expression was done on a sixty patients who complained from primary papillary superficial transitional cell carcinoma (TCC) of the urinary bladder (Stage Ta-T1).Their predicting role for recurrence, progression, progression-free survival (PFS), and recurrence-free survival (RFS) was assessed. RESULTS: High Sox2 expression was observed in 55% of NMIBC cases, and it was significantly associated with the tumor size, grade, and stage (p <0.001 for each). High YAP1 was noted in 33.3% of the cases, and its expression was significantly associated with the tumor size, grade, and stage (p <0.001 for each). Strong IMP3 expression was detected in 45% of the cases, and it was associated with the tumor size, grade, and stage (p < 0.001 for each). Analysis of follow-up period revealed that NMIBC with high Sox2, high YAP1, and Strong IMP3 expression exhibited a potent relation with tumor recurrence, progression, and shorter RFS & PFS.CONCLUSIONS: High Sox2, high YAP1, and strong IMP3 could be considered as adverse prognostic factors of tumor recurrence and progression in NMIBC, and these patients should be followed carefully. Therefore, we suggest that Sox2, YAP1 and IMP3 should be considered and evaluated during the selection of the appropriate management strategy for NMIBC patients. Keywords: Sox2; YAP1; IMP3; Immunohistochemistry; Non-muscle-invasive bladder cancer; Prognostic markers