Objective：To investigate the expression of tripartite motif 21（TRIM21） in pancreatic cancer and its relations with clinico－pathological features，prognosis and immune infiltration. Methods：Oncomine and GEPIA databases were applied to analyze the mRNA expression level of TRIM21 in pancreatic cancer. Gene set enrichment analysis（GSEA） was used to predict the possible signaling pathways that TRIM21 may be involved in. TIMER database was used to analyze the correlation between TRIM21 expression level in pancreatic cancer and the infiltration abundance of immune cells，and the results were validated by Kaplan-Meier Plotter database. Immunohistochemistry（IHC） test was used to detect the protein level of TRIM21 in 87 cases of pancreatic cancer tissues and 36 cases of para-carcinoma tissues，and to analyze its relations with clinicopathological features and prognosis. Results：TRIM21 was signifi－cantly overexpressed in pancreatic cancer and negatively correlated with relapse-free survival（P=0.041）. GSEA analysis confirmed that TRIM21 was involved in immune-related signaling pathways in patients with pancreatic cancer. TIMER database analysis showed that the expression level of TRIM21 in pancreatic cancer was positively associated with B cells（P=7.87e-06），CD8+ T cells（P=1.18e-04），macrophages（P=1.43e-02），neutrophils（P=2.01e-07） and dendritic cells（P=9.52e-09） infiltration levels. Kaplan-Meier Plotter database analysis showed that pancreatic cancer patients with high concentration of immune cells with high expression of TRIM21 had lower overall survival than those with low expression of TRIM21. IHC analysis indicated that TRIM21 was significantly overexpressed in pancreatic cancer tissues，and the prognosis was lower in patients with high expression of TRIM21 than those with low expression of TRIM21（HR=1.725，P=0.033）. Compared with low expression of TRIM21，there were significant differences in the serum CEA level（P=0.000），CA-199 level（P=0.002） and AJCC pathological stage（P=0.004），N stage（P=0.010），M stage（P=0.006），and tissue differentiation（P=0.000） in the pancreatic cancer patients with high expression of TRIM21. The multivariate regression analysis showed that CA-199 level（P=0.008），N stage（P=0.028） and tumor size（P=0.049） were independent factors affecting the overall survival in patients with pancreatic cancer after surgery. Conclusion：TRIM21 is highly expressed in pancreatic cancer and marks a poorer clinical prognosis and promotes the development of pancreatic cancer by modulating immune infiltration affecting the tumor microenvironment.