The serine/threonine-protein kinase PFTAIRE 1 (PFTK1) is a member of the cyclin-dependent kinase family that is highly expressed in several malignant tumors, including hepatocellular carcinoma, esophageal, breast and gastric cancers, and glioma. It contributes to tumor progression and influences tumor prognosis. However, the expression and clinicopathological significance of PFTK1 in human colorectal cancer (CRC) remain to be elucidated. The present study aimed to examine the expression of PFTK1 and to evaluate the clinical significance of its expression in human CRC. Reverse transcription-quantitative polymerase chain reaction was performed on 10 fresh CRC and 10 surrounding normal tissue samples to detect and compare the expression of PFTK1 mRNA in CRC and normal colorectal tissues. Immunohistochemistry was performed on 179 CRC tissue specimens and 47 control samples of normal colorectal lesions to characterize the expression of PFTK1 protein. Kaplan-Meier overall survival (OS) rate and Cox regression analyses were performed to evaluate the prognosis of patients with CRC. The expression of PFTK1 mRNA in CRC tissues (1.433 +/- 0.168) was significantly higher compared with normal tissues (0.853 +/- 0.107; t=1.97 ('t' was the value obtained from quantification of the mRNA data, following a paired t-test), P=0.008). High PFTK1 expression in cancerous cells was detected in 92 of the CRC specimens (51.40%), and high levels of PFTK1 were associated with tumor node metastasis (TNM) stage (P=0.042), tumor classification (P=0.022) and preoperative carcinoembryonic antigen (CEA) level (P<0.001). Kaplan-Meier OS rate and Cox regression analysis revealed that high PFTK1 expression level (hazard ratio (HR)=1.999; P=0.019) was an independent prognostic factor of CRC patients. The degree of differentiation (HR, 0.368, P=0.003), TNM classification (HR, 2.118, P=0.001) and preoperative CEA level (HR, 2.302, P=0.003) were also predictors of the prognosis of patients with CRC. The present study suggested that PFTK1 may be a potential anticancer target and prognostic marker in patients with CRC.