〔Abstract〕 Objective To explore the function and role of UFL1 in maintaining the genomic stability of prostate cancer（PCa）cells. Methods The differentially expressed genes in the two groups of data with high and low PCa aneuploidy levels were analyzed using bioinformatics and RNA-seq. Gene set enrichment analysis（GSEA）was conducted to identify biological processes associated with UFL1. Functional assays，including immunofluores⁃ cence，CCK-8，colony formation，wound healing，and apoptosis assays，were employed to evaluate the effects of UFL1 on the mitotic progression，proliferation，migration，and apoptosis of PCa cells.Results Integrated bioinfor⁃matics and RNA-seq analyses identified that UFL1 showed low expression in PCa tissues and cell lines with high ge ⁃ nomic instability characteristics. GSEA further indicated an association between UFL1 and mitotic biological pro⁃ cesses. Subsequent immunofluorescence experiments demonstrated that UFL1 depletion increased the frequency of chromosomal segregation errors during mitosis in PCa cells. Functional in vitro assays，including CCK-8，colony formation，wound healing，and apoptosis analysis，consistently revealed that after the knockdown of UFL1 in PCa cells，the proliferation activity and migration ability of the cells showed a weakened trend，while the apoptosis rate showed an upward trend. Conclusion UFL1 maintains genomic stability by precisely regulating the mitotic pro ⁃ cess of PCa cells，thereby promoting the proliferation of PCa cells.