Mitochondrial transcription factor A (mtTFA) is necessary for both the transcription and maintenance of mitochondrial DNA (mtDNA). The present study investigated the relationship between clinicopathological factors, prognosis and the immunohistochemical expression of mtTFA in the tumors of patients diagnosed with primary colorectal cancer (CRC). Surgical specimens from 105 colorectal patients were immunohistochemically stained using a polyclonal anti-mtTFA antibody. The relationships among the mtTFA expression, clinicopathological factors and prognosis were evaluated. A total of 47 (44.8%) of the 105 patients with CRC were determined to have positive mtTFA expression. The positive expression of mtTFA significantly correlated with lymph node metastasis, distant metastasis and advanced TNM staging. On the other hand, negative mtTFA expression showed a tendency to correlate with high Ki-67 index. The survival of patients with positive mtTFA expression was significantly worse than that of patients with negative mtTFA expression. The positive mtTFA expression appears to be a useful marker for tumor progression and poor prognosis in patients with CRC.