Colorectal cancer (CRC) is one of the most common malignancies worldwide. Tripartite motif-containing 29 (TRIM29) is a member of TRIM proteins family, which plays diverse physiological and pathological roles in humans. Recent studies found that TRIM29 expressed highly in CRC and promoted cell growth in vitro. However, its function in the metastasis of CRC has not been studied. In the present study, we confirmed the previous report that TRIM29 was upregulated in CRC tissues and high levels of TRIM29 expression were associated with poor overall survival of patients. Moreover, TRIM29 knockdown significantly reduced cancer cell proliferation via notably inducing cell cycle arrest and cell apoptosis. Silencing of TRIM29 significantly inhibited the migration and invasion ability of CRC cells. The protein levels of apoptosis-, migration- and invasion-related proteins were also changed after TRIM29 knockdown. Furthermore, phosphorylation levels of JAK2 and STAT3 were clearly reduced in TRIM29 knockdown cells, indicating a possible mechanism underlying its effects on colorectal carcinogenesis. Collectively, TRIM29 may exert oncogenic effects in CRC cells via regulating JAK2/STAT3 signaling.