Pancreatic cancer (PC) is a commonly malignant tumor with a 5-year survival rate of only 10%.1 Cuproptosis is a newly discovered cell death mechanism closely associated with the development of tumors. This study mainly aimed to investigate cuproptosis-related genes (CRGs) and found the marker genes to construct a prognostic model for PC patients. Meanwhile, we explored their roles in immune infiltration and their relationship with drug sensitivity. After comparing the expression patterns of ten CRGs, we found these genes were differently expressed between the tumor and normal tissues. Then we further performed functional enrichment analysis, cluster analysis, and immuno–infiltration correlation analysis. We found that cyclin-dependent kinase inhibitor 2A (CDKN2A) had the highest mutation frequency and was significantly down-regulated in tumor samples. Besides, high expression of dihydrolipoamide S-acetyltransferase (DLAT) was associated with a worse prognosis by Kaplan–Meier survival analysis. Finally, we constructed a prognostic model based on these CRGs. In the 1-year, 3-year, and 5-year receiver operator characteristic curves, the predictive accuracy of evaluation of the area under a receiver operating characteristic curve was 0.638, 0.690, and 0.796, respectively. Besides, we identified 30 potential gene mutation regulators and obtained the differences in immune microenvironment and drug sensitivity in different risk groups, which provided references for PC prediction, immunotherapy, drug therapy, and gene therapy.