Protein tyrosine phosphatase 1B (PTP1B) is a non-transmembrane protein tyrosine phosphatase that has been implicated in cancer pathogenesis. However, the expression level and the role of PTP1B in the development and prognosis of colorectal cancer (CRC) remain unclear. In this study, the expression of PTP1B in CRC tissues and matched noncancerous tissues were detected by using immunohistochemistry, real-time PCR and Western blotting. The correlations between PTP1B expression level and clinicopathologic characteristics and patient survival were analyzed. We found that PTP1B expression was significantly higher in CRC tissues compared with matched non-tumour tissues. Statistical analysis showed that the PTP1B expression was correlated with tumor differentiation, tumor invasion, lymph node metastasis, and TNM stage. Patients with higher expressions of PTP1B had the lower survival (P = 0.012). Taken together, our results suggest that PTP1B expression might play a critical role in the progression of CRC and may serve as a valuable prognostic biomarker for CRC.