Colorectal　cancer　(CRC)　is　a　highly　prevalent　and　fatal　malignancy,　with　incidence　and　mortality　rates　rising　globally.　While　elevated　UBC9　expression　has　been　implicated　in　various　cancers,　its　specific　role　in　CRC　remains　poorly　understood.　This　study　aims　to　investigate　the　expression　levels,　prognostic　significance,　and　functional　roles　of　UBC9　in　CRC.　We　assessed　the　expression　and　prognostic　value　of　UBC9　mRNA　and　protein　in　colorectal　cancer　separately　using　multiple　databases　and　immunohistochemical　techniques.　Additionally,　in　vitro　functional　assays　and　in　vivo　zebrafish　tumor　models　were　employed　to　elucidate　the　role　of　UBC9　in　CRC　cell　proliferation,　migration,　invasion,　and　chemoresistance.　UBC9　expression　was　significantly　upregulated　in　CRC　tissues.　Elevated　UBC9　levels　were　associated　with　poor　prognosis　in　chemotherapy-treated　CRC　patients.　Gene　Set　Enrichment　Analysis　revealed　that　pathways　related　to　MYC　targets,　DNA　repair,　and　oxidative　stress　response　were　enriched　in　groups　with　high　UBC9　expression.　Immune　profiling　indicated　reduced　infiltration　of　CD4+　memory-activated　T　cells　and　NK　cells　in　tumors　with　elevated　UBC9　levels.　Functional　assays　demonstrated　that　UBC9　knockdown　inhibited　CRC　cell　proliferation,　migration,　and　invasion,　and　sensitized　cells　to　oxaliplatin,　which　was　further　validated　using　zebrafish　xenograft　models.　UBC9　is　crucial　for　CRC　progression,　genomic　instability,　and　chemoresistance.　It　represents　a　potential　prognostic　biomarker　and　therapeutic　target,　particularly　for　enhancing　chemotherapy　efficacy　in　CRC　patients.