ObjectiveTo investigate the expression of tripartite motif 21 (TRIM21) in gastric cancer tissues and its relationship with clinical pathological characteristics and clinical prognosis.MethodsPublic database was used to analyze the expression level of TRIM21 in gastric cancer tissues and the relationship between its expression and clinical prognosis. Gene set enrichment analysis (GSEA) was used to analyze the signaling pathways that TRIM21 might participate in. The expressions of TRIM21 in 80 gastric cancer tissues and 30 para-cancer tissues were detected by immunohistochemical staining, and the relationship between TRIM21 expression and clinicopathologic characteristics was analyzed.ResultsTRIM21was significantly low-expression in gastric cancer tissues, and the clinical prognosis of patients with low TRIM21 expression was significantly worse (P<0.05); GSEA showed that TRIM21 was involved in the regulation of helper T cell differentiation in gastric cancer patients (P<0.000 1, FDR<0.000 1).ConclusionsTRIM21 is poorly expressed in gastric cancer tissues and indicates the poor clinical prognosis. Moreover, TRIM21 is involved in the regulation of helper T cell differentiation and has a negative regulatory effect on the occurrence and development of gastric cancer.