This study aimed to explore the role of the UDP glucuronosyltransferase 1 family, polypeptide A6 (UGT1A6), in pancreatic cancer, focusing on its expression patterns, clinical significance, impact on tumor progression, and potential involvement in immune evasion.UGT1A6 expression across multiple cancer types was analyzed using TNMplot, GEPIA, and The Cancer Genome Atlas (TCGA) databases. Functional experiments, including western blotting, qRT-PCR, CCK-8, and Transwell assays, were performed on pancreatic cancer cell lines to assess their proliferation and migration capabilities. Single-cell data and cell-cell communication analyses using CellChat were conducted to investigate UGT1A6's influence on the immune microenvironment.UGT1A6 expression was significantly upregulated in pancreatic cancer tissues and correlated with poor overall survival (P = 0.0095), advanced TNM stage, and KRAS and TP53 mutations. Functional experiments revealed that UGT1A6 knockdown markedly suppressed the proliferation and migration of pancreatic cancer cells. Immune analysis demonstrated a positive correlation between UGT1A6 and immunosuppressive molecules (CD274, PDCD1LG2, HAVCR2, and TGFBR1) and specific immune cell infiltration patterns, indicating a potential role in promoting immune evasion. Single-cell analysis further showed enhanced communication between UGT1A6-expressing tumor epithelial cells and immune cells, which might impair antitumor immune responses.UGT1A6 acts as a key driver of pancreatic cancer progression and immune evasion, and is emerging as a promising prognostic biomarker and therapeutic target. Future studies should focus on clarifying the detailed molecular mechanisms and validating their clinical utility in precision therapy.© 2025. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).