Background: In colorectal cancer (CRC) patients, different primary tumor locations caused distinct prognosis and clinicopathological features. It is necessary to identify specific tumor markers according tumor site. Our previous work has identified differentially expressed genes between CRC and adjacent normal tissues, in which only TRIM29 was differently expressed between right colon cancer (RCC) and left colon cancer (LCC) patients. Rectal cancer (RECC) was not included in this latter study and the effects of TRIM29 on the survival with RCC and LCC patients were not investigated. This study further verified TRIM29 expression through Gene Expression Omnibus (GEO) database and our retrospective study. The role of TRIM29 on survival according tumor sites was also explored. Furthermore, the molecular mechanisms of TRIM29 were explored. Methods: The GEO dataset was used to confirm the differential expression of TRIM29 in proximal and distal cancers. Moreover, TRIM29 were assess using immunohistochemistry (IHC) in 227 cases to observe the correlation between TRIM29 and tumor site. The relationship between TRIM29 and the clinicopathologic features was investigated according tumor sites. Furthermore, the disease-free survival (DFS) and overall survival (OS) was analyzed using the Kaplan-Meier method to assess the prognostic value of TRIM29. Finally, bioinformatics analysis was used to explore the molecular mechanisms. The Tumor Immune System Interactions and Drug Bank database (TISIDB) was used to analyze the correlations between TRIM29 expression and tumor immune functions. The correlation of TRIM29 with tumor infiltrating lymphocytes or mismatch-repair-proficient/mismatch-repair-deficient (pMMR/dMMR) status was also investigated. Results: TRIM29 expression was significantly higher in patients with RCC (P<0.001). RCC patients with high TRIM29 tended to be older, male, in stage III-IV, with N+ staging, and intestinal obstruction (P<0.001, P<0.001, P<0.001, P<0.001, and P=0.010, respectively). High TRIM29 expression was associated with an increased risk of recurrence/metastasis and death, only in RCC patients (P=0.020 and P<0.001). Functional annotations and immune activity analysis showed that TRIM29 is related to tumor infiltrating lymphocytes and immune dysfunction. Conclusions: TRIM29 plays varying roles in patients with different tumor sites. TRIM29 is correlated with the clinicopathological features and prognosis in RCC patients. Indeed, TRIM29 may serve as a new biomarker for RCC patients.