Colorectal cancer (CRC) remains one of the most common cancers worldwide. HS1-associated protein X-1 (HAX-1) has been highlighted as an important marker in many types of cancers. However, little is known about the role of HAX-1 in CRC. The aim of this study was to analyze the correlation of HAX-1 expression with the clinicopathological features of CRC. The protein and mRNA levels of HAX-1 were examined by immunohistochemistry (IHC) and real-time quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) in CRC tissues and adjacent noncancerous tissues. Survival curves were made with follow-up data. The relations of the prognosis with clinical and pathological characteristics were analyzed. Using IHC and RT-qPCR, we showed that HAX-1 expression was significantly higher in CRC tissues than in adjacent noncancerous tissues (P < 0.05). High HAX-1 expression was significantly associated with lymph node metastasis (P = 0.034) and tumor (T) node (N) metastasis (M) stage (P = 0.028) of patients with CRC. The Kaplan-Meier survival curves indicated that overall survival was significantly worse in CRC patients with HAX-1 overexpression. Multivariate analysis showed that high HAX-1 expression was an independent predictor of overall survival. In conclusion, our data for the first time provide a basis for the concept that overexpression of HAX-1 may contribute to the malignant progression of CRC and predict poor prognosis for patients with this disease. HAX-1 might be an important marker for tumor progression and prognosis, as well as a potential therapeutic target of CRC.