Tripartite motif-containing 29 (TRIM29), also known as ataxia-telangiectasia group D, is structurally a member of the tripartite motif family of proteins, which characterized by the conserved RING finger, B-box, and coiled-coil domains. TRIM29 functions as an oncogene or a tumor suppressor depending on the tumor types. In this study, we aim to evaluate whether TRIM29 affects the tumorigenesis and progression of colorectal cancer. The expression of TRIM29 was investigated using real-time PCR in 40 pairs of colorectal cancer tissues and immunohistochemistry on a tissue microarray containing 203 cases of primary colorectal cancer paired with non-cancerous tissues. Down-regulation of TRIM29 was achieved by transient transfection in RKO cell lines, and the effects of TRIM29 on tumor proliferation were evaluated by MTT and plate colony formation assays. Results indicated that TRIM29 expression was much higher in colorectal cancer tissues and significantly associated with the depth of tumor invasion, lymph node metastasis, distant metastasis, histological differentiation, vascular invasion, ki-67 index, and advanced tumor stage. Patients with TRIM29-positive tumors had a higher recurrence rate and poorer survival than patients with TRIM29-negative tumors. In multivariate analyses, the TRIM29 expression was an independent factor for determining colorectal cancer prognosis after surgery. Moreover, down-regulation of TRIM29 inhibited tumor cell proliferation in vitro. In conclusion, TRIM29 plays an important role in promoting colorectal cancer progression. Our findings suggest that TRIM29 may serve as a novel biomarker for tumor recurrence and survival for colorectal cancer patients.