Background:Tripartite motif-containing protein 21 (TRIM21), a member of the ubiquitin ligase family, makes a significant contribution to the ubiquitination of multiple tumor marker proteins associated with tumor cell proliferation, metastasis and selective apoptosis. As the research further develops, an increasing number of studies have manifested that the TRIM21 expression level can be considered an indicator of cancer prognosis. However, the interrelationship between TRIM21 and multiple forms of carcinogens has not been demonstrated in a meta-analysis.Methods:We performed a systematic literature retrieval in various electronic databases including PubMed, Embase, Web of Science, Wanfang and China National Knowledge Infrastructure. Besides, the hazard ratio (HR) and the pooled relative risk (RR) were integrated in the assessment of cancer incidence and cancer mortality by Stata SE15.1. Additionally, we used an online database based on The Cancer Genome Atlas (TCGA) to further validate our results.Results:A total of 17 studies were included, totaling 7239 participants. High expression of TRIM21 was significantly correlated with better OS (HR = 0.74; 95% CI: 0.57–0.91;P< .001) and progression-free survival (PFS) (HR = 0.66; 95% CI: 0.42–0.91;P< .001). We found that high TRIM21 expression predicted significant impact on clinical characteristics like decreased lymph node metastasis (RR = 1.12; 95% CI: 0.97–1.30;P< .001), tumor stage (RR = 1.06; 95% CI: 0.82–1.37;P< .001) and tumor grade (RR = 1.07; 95% CI: 0.56–2.05;P< .001). However, TRIM21 expression had no significant impact on other clinical characteristics such as age (RR = 1.06; 95% CI: 0.91–1.25;P= .068), sex (RR = 1.04; 95% CI: 0.95–1.12;P= .953), or tumor size (RR = 1.14; 95% CI: 0.97–1.33;P= .05). Based on the Gene Expression Profiling Interactive Analysis (GEPIA) online analysis tool, TRIM21 was significantly downregulated in 5 cancers while significantly upregulated in 2 cancers, and the descending expression of TRIM21 predicted shorter OS in 5 cancers, worse PFS in 2 malignancies, while the elevated expression of TRIM21 predicted shorter OS and worse PFS in 2 carcinomas.Conclusions:TRIM21 could serve as a new biomarker for patients with solid malignancies and could be a potential therapeutic target for patients.