Abstract: Objective To investigate the expression and clinical significance of GATA-3 and H3K27me3 in Tibet with bladder urothelial carcinoma (BUC). Methods BUC and normal bladder tissues were collected retrospectively from January 2016 to December 2021 in the People's Hospital of Tibet Autonomous Region. The expression of GATA-3 and H3K27me3 in both tissues was detected by immunohistochemical method, and the clinical and pathological characteristics were statistically analyzed. Results A total of 70 patients with BUC were selected, including 51 males and 19 females, with an average age of (60.5± 12.0) years. At the same time, 20 normal bladder tissue samples were collected during the same period. All cases were Tibetan patients. Immunohistochemistry results showed that the high expression rate of GATA-3 in BUC and normal bladder tissue was 70% (49/70) and 100% (20/20), respectively. High expression of GATA-3 was associated with male, low pathological grade, and non invasive tissue (P<0.05). The high expression rate of H3K27me3 in BUC and normal bladder tissue was 45.7% (32/70) and 20% (4/20), respectively. High expression of H3K27me3 was only associated with male (P<0.05). Conclusions The expression of GATA-3 is down regulated in patients with BUC in Tibet, and significantly down regulated with the increase of tumor grade, suggesting that GATA-3 may be involved in the occurrence and development of BUC and related to its malignancy, providing a reference for clinical diagnosis and treatment and judging disease prognosis. The expression of H3K27me3 in BUC in Tibet is higher than that in normal bladder tissue, suggesting that H3K27me3 may be a new immune marker for diagnosis of bladder urothelial carcinoma.