Objective To investigate the expressions of hypoxia-inducible factor-1α (HIF-1α) and caudal homeobox gene 2 (CDX2) in colorectal adenocarcinoma, and the relationships between them and the clinicopathologic factor of colorectal adenocarcinoma. Methods The expressions of HIF-1α and CDX2 were detected by immunohistochemistry in 62 specimens of colorectal adenocarcinoma and 20 specimens of normal colorectal mucosa tissue. The correlation between the expressions of HIF-1α and CDX2 was analyzed by Spearman rank correlation analysis. Results The positive rates of HIF-1α expression in normal colorectal mucosa tissue and colorectal adenocarcinoma were 5.0% （1/20） and 62.9% （39/62）, CDX2 were 95.0% （19/20） and 69.4% （43/62）, the differences of positive rate between different tissues were significant （Plt;0.05）. In colorectal adenocarcinoma, the expression of HIF-1α or CDX2 was related to tumor differentiation, lymph node metastasis, and Dukes staging (Plt;0.05). There was a negative correlation between HIF-1α and CDX2 expressions in colorectal adenocarcinoma （r=－0.293 2，Plt;0.05）. Conclusions The up-regulation of HIF-1α and down-regulation of CDX2 may be involved in the genesis of colorectal adenocarcinoma， and there is a negative correlation between the two kinds of protein. HIF-1α may participate in modulation of CDX2 expression and lead to accelerate the progression of colorectal carcinoma.