This study was carried out to assess the efficacy of urinary hepatoma up-regulated protein (HURP) RNA in bladder cancer diagnosis and its relation to bilharziasis. Voided urine samples and blood were collected from 344 consecutive participants: 211 patients diagnosed with bladder cancer, 71 patients with benign urological disorders and 62 healthy volunteers. Serologic assessment of schistosomiasis antibody in sera, urine cytology and estimation of HURP RNA by reverse transcription polymerase chain reaction in urothelial cells was carried out in all samples. HURP RNA expression showed a significant difference among the three investigated groups. The best cutoff point for HURP RNA was determined as 0.0132 at 78.67 % sensitivity and 94 % specificity. The sensitivity of urine cytology was improved when combined with HURP RNA in detection of early stage (77.3 %), low grade (85.3 %) and bilharzial bladder cancer (78.1 %). Detection of urinary HURP RNA is a useful non-invasive test for early detection of bladder cancer and bilharzial bladder cancer and it improves sensitivity of urine cytology up to 91 %.