To investigate the expression status of periostin in colorectal cancer (CRC) to lay a foundation for managing this disease.Periostin expression status was detected by immunohistochemistry staining in 720 CRC specimens. The relationship between the periostin protein and clinicopathological factors and prognosis was subsequently determined.The periostin protein was expressed significantly higher in CD133+ tumor cells compared to CD133- tumor cells. Positively expressed periostin was observed in 218 (30.28%) of the 720 cases. Spearman correlation analysis showed that periostin expression has a linear correlation to the tumor size, histological type, lymph node metastasis, TNM stage, and postoperative liver metastasis (p=0.02, 0.035, 0.001, 0.001, and 0.001, respectively). Multivariate analysis showed that histological type, lymph node metastasis, TNM stage, and periostin were found to be related to liver metastasis (p=0.01, 0.035, 0.01, and 0.001, respectively). In the Cox regression test, the histological grade, Lymph node metastasis, TNM stage, and periostin were detected as independent prognostic factors (p=0.01, 0.001, 0.001, and 0.001, respectively).Periostin was found to be related to the liver metastasis of CRC and may be a potential target for CRC.