Ankyrin repeat and SOCS box-containing 9 (ASB9) is involved in the negative regulation of cytokine signaling. However, its biological function is largely undefined. The aim of this study was to assess the value and role of ASB9 as an indicator of prognosis in colorectal cancer (CRC). In order to demonstrate the importance of ASB9 expression for predicting the prognosis of CRC, we analyzed the ASB9 mRNA expression in 125 paired cases of CRC and non-cancerous regions and the protein expression by immunohistochemistry. To investigate the role of ASB9 in vitro, we performed proliferation and invasion assay with small interfering RNA against ASB9. ASB9 mRNA expression was higher in CRC tissue than corresponding normal tissue (P=0.0282). Patients expressing low levels of ASB9 had a poorer overall survival rate than those expressing high levels (P=0.0301), indicating that decreased ASB9 expression was an independent prognostic factor. The immunohistochemical study revealed that ASB9 was predominantly expressed in cancer cells. A multivariate analysis showed that ASB9 expression status was an independent prognostic factor of overall survival (relative risk, 4.09; 95% confidence interval, 1.47-11.88; P=0.007). In an invasion assay, ASB9 siRNA-transfected cells showed significantly high invasiveness. The results of the present study suggest that ASB9 is a useful prognostic marker for CRC.