〔Abstract〕 Objective To investigate the expression of the Y chromosome gene lysine-specific demethylase 5D(KDM5D) in male bladder cancer and its effects on cancer progression, thereby explaining gender-related prognostic differences in bladder cancer. Methods Bioinformatics analysis was conducted to identifyKDM5Das a differentially expressed Y chromosome gene with prognostic significance in bladder cancer based on data from the TCGA database. The expression ofKDM5Din bladder cancer cell lines, collected clinical bladder cancer tissues, and adjacent normal epithelial tissues were examined using quantitative Real-time PCR(qPCR), Western blot, immunofluorescence, tumor microenvironment analysis, and bioinformatics pathway analysis. The effects ofKDM5Don bladder cancer cell proliferation and migration were validated through cell experiments followingKDM5Dknockdown and overexpression. Additionally, clinical data onKDM5Dexpression in bladder cancer tissue arrays were statistically analyzed in relation to metastasis and recurrence. Results KDM5Dwas generally downregulated in male bladder cancer but exhibited variable expression in different bladder cancer cell lines and between recurrent and non-recurrent bladder cancers. Overexpression ofKDM5Dinhibited tumor cell proliferation and migration, and lowerKDM5Dexpression was associated with higher recurrence and metastasis rates. Bioinformatics analysis suggested thatKDM5Dmight influence tumor metastasis or recurrence by affecting immune cell aggregation and epithelial-mesenchymal transition. Conclusion KDM5Dis a protective gene specific to male bladder cancer and may be associated with the generally better prognosis observed in male compared to female bladder cancer patients.